How to cite: Shore, Neal D. “A Primer on Alternative Payment Models: The Need for a Urology APM” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/a-primer-on-alternative-payment-models-the-need-for-a-urology-apm/

Summary:

Neal D. Shore, MD discusses a different angle of the urologists experience: the need for alternative payment models (APMs) and impact of the Merit-Based Incentive Payment System (MIPS). Many urologists do not have APM options, but the Large Urology Group Practice Association (LUGPA) is trying to change this. Dr. Shore believes an understanding of the systems in place and the need for a urology APM is important for urologists to know.

The Present and Future of LUGPA – Transcript

Click on slide to expand

A Primer on Alternative Payment Models: The Need for a Urology APM

So this whole concept of APM development or alternative payment models and why do we need one, and that probably, if I could get that message across, that may be one of the best things I can do in this presentation. Remember that the Affordable Care Act came after MACRA was already approved by Congress with overwhelming bipartisan support.

USPSTF

And the reason why we have MACRA is because we were for 20 some plus years kicking the can down the road with the sustained growth rate, or the SGR, which was a proverbial sort of Damocles over all of us that we were going to have marked reductions in our Medicare reimbursement. So finally when they got, you know, they did the MACRA, which got rid of the SGR but what we brought on instead with MACRA is this whole new way of getting reimbursement methodologies and metrics (ie, the MIPS merit incentivized based system) and APMs. So I’m going to talk a little bit more about that.

So which of the following is true? Over 60% of urologists are exempt from MIPS reporting. MIPS penalties apply to Part B drug revenue. Approximately 20% of urologists nationwide participate now in APMs. And physician groups of 10 or more may report MIPS as their tax ID number rather than an individual NPI.

Background

So background—why do urologists need an APM? The bottom line why we need an APM is it comes down to reimbursement, pure and simple, and hopefully I’ll be able to explain that to you.

MACRA Provides for 4 Different “Statuses

So MACRA provides these four different statuses so to speak for you and your clinic or your partnership, or your employment. You could be in the MIPS only, where these are practices who are only participating in MIPS and have no APM model. MIPS with an APM are sort of a hybrid, and I’ll show you why these are all relevant as it relates to your reimbursement or lack thereof. There’s a partial qualifier, where the practice is achieving partial qualifying thresholds, and you have some upward adjustments of the MIPS as well as in your APM model, and then you’re in a qualified for an APM bonus, and these are practices that are participating in a true eligible APM, and they receive this 5% bonus as well as the APM model payments.

APM Requirements

So getting back you remember there are these four new metrics that came in with the MIPS that replaced other things such as PQRS, and meaningful use, and value-based modifiers, and so once again there is this whole word salad of acronyms that you have to have a team to help you adjust to and you’re seeing it now a lot—largely in your EHRs.

So CMS estimates that a little over 12,000 physicians, 1.1% in the entire United States, will qualify for an APM in 2017. Mind you, the MACRA legislation came out several years ago, and this is—we’re not making a lot of rapid progress here. Now, why is that important? Well, if you look down at this table, what you are seeing is that in order to get the requirements for this APM incentive, which is where all of the bonus pool of money is, and going from 2017 into 2018, ultimately to 2022, where you are going to receive this and be eligible to receive this is if you qualify for an APM, and right now only two urology practices that I’m aware of in the entire United States are part of an APM.

So CMS estimates that 88 urologists of the roughly 10,000 will qualify as an APM in 2017. So bing, bing, bing light goes on, government is telling you with this chart this is where the bonus pool of money is, and yet we’re being clearly excluded from it.

MIPS is not in Practice Control

If you don’t care about it, then none of this will be germane to you, but if you’re running a clinic, if you’re running an academic department, if you’re running a practice, if you’re any one of these things, and you have a lot of employees, these become very important. So when fully implemented, the resource use to be 30% of your MIPS score eventually right now the resource use is the cost that you’re generating. Now, this is all basically comes up as—you don’t report it. This comes through CMS claims data, and CMS will use this to attribute patients to physicians through your tax ID number if you have greater than 25, not 10, greater than 25 eligible physicians in your group. This helps you get to APM reporting. It’s a two-step attribution process.

Now, this attribution process can sometimes, when I’ve heard people talk about it, cause you a sort of deer in the headlights view on it, is who is primarily doing the majority of the patient care? So is there a primary care provider who has the plurality of the ENM codes designated as referable to the primary care? You’d be amazed how many patients you might, if you look at your own data, only come to see you as the urologist, and thus you can get attributable to their total cost of care if you have seen somebody for one, or two, or three urinary tract infections during the year or asymptomatic microhematuria, and you are part of this, and low and behold that same patient who may have other kind of drug-seeking behavior or weird comorbidities ends up hospitalized and getting all of these complications. This person then becomes attributable to you and your group if they’ve not seen anyone else.

So that’s really the final bullet at the bottom one. How do I change it?

MIPS is not in Practice Control

MIPS is not in the practice control. The physician to whom the patient is attributed is assigned all of the cost from that patient, so this now starts to speak to this concept of bidirectional risk or two-sided risk adjustment, which is a big theme of moving the risk away from the payer to the provider (ie, us). So all cost for a patient, in patient, outpatient, ancillary Part B drugs, can be attributed regardless of who provided the service, so if you are the considered the plurality of service and then they go in and have a dissecting aneurysm and you are the attributable provider, that all goes back to your bottom line, and can really affect the cost calculation on a normative curve.

MIPS Performance Categories:  Resource Use

So the MIPS performance categories, the resource use, this is the part that they’re looking through in claims data, and it can also be—it’s 98% of it is attributed to ENM visits. This is from Deepak’s own practice, and he looked at his data and IMP, integrated medical physicians, and they saw patients in only about 20% of their actual hospitalizations. So the median number of ENM visits to generate attribution to their practice.

And he actually shared with me in his own personal review, and he’s primarily doing largely administrative work, but he still sees patients, and he had this woman who came in and who he had seen for a few urinary tract infections, relatively uncomplicated, turns out she ended up getting very sick unrelated to anything with the urinary tract, and his score based upon that in his review put him and his group of over 80 physicians as one of the highest resource uses in his group despite the fact that he has one of the lowest patient volumes.

MIPS Exemptions Not Equal Across Specialties

So MIPS exemptions are not equal across the specialties. This is actually just was revised by Deepak prior to coming here so CMS has increased what’s called the low-volume threshold exclusion, and as a result, 63% of all Medicare clinicians will be exempt from MIPS in 2018, but look how high up we are as a specialty as being eligible for the MIPS in comparison to some of the other specialties. So there’s this sort of odd conundrum that we really need to follow up and be cognizant of.

MIPS Updates and Adjustments

Now, one of the things that just came out in all of this was a change in the rule of—and taking a little bit of the teeth out of the penalty and the bonus for this year so that it’s really not going to be as Draconian as it appeared to be. But if some of the updates and the adjustments. So if you’re in this scoring threshold and you get a score for those four different metrics within the MIPS if you are less than this 25% threshold versus 25% to the above, which is vastly increased, they’ve taken a lot of the teeth out of this. And so there’s a small percentage of folks who will be above the threshold for the composite score but even the pool of money, which I think is about $500 million if I’m not mistaken has to be divided amongst all participating physicians.

So it’s normative. It’s not criteria-based scoring. It’s all physicians, not just urology. And there’s a huge exempting of many physicians who pose challenges to so many of us. So we’re being in a big pool with primary care physicians and everybody else.

MIPS Payment Adjustment to Part B Drugs

So this has to do with drugs, and if you’re into systemic therapies, and if you’re giving a lot of oncologic care, just pay attention as you can see to the far right, how if you’re in the penalty situation and you’re giving Part B drugs, and ASP percent as opposed to—and you’re in the bonus pool, so if you’re getting 4.4% because of the sequestration, it’s not really a true 6%, you could get, if you’re in the bonus pool, you could get an additional 11% on say a $100,000 treatment versus getting a negative 3.3%. So in a large practice, whether you are medical oncologists or urologists, and as more and more drug therapies become intermixed in all of our GU oncology, this becomes extremely relevant.

So by 2022, which is not that far off, low performers versus high performers, there’s a huge swing in just Part B drugs alone.

Economics of MACRA Statuses

This is important for our industry colleagues to recognize. Now, this just tells you if you look at the top kind of light Carolina blue color, but MIPS with APM that is your maximum gain. That’s where you’re going to do the best in terms of the economic status and you can see all of those different kinds of categories that I mentioned earlier.

So why am I telling you about this? I’m telling you about this because we at LUGPA put forward an APM this year.

Summary

There are no APM vehicles specific to urology practices right now in the entire country. And less than 1% of urologists qualify for an APM. The MIPS exemption is unequally distributed, only 2.1% of urologists are exempted, only 2.1. The remaining physicians we compete against the top, all of the other top performers. Succeeding in MIPS is ultimately out of your practice control. Your resources are based on claims data. You’ll get penalties potentially under Part B medications if you’re not—if you’re not monitoring your metrics, and it’s the MIPS APM category that has to be obtained, and right now we can’t obtain it because it’s not within accessible reach. So we have put forward an APM at the LUGPA level.

Selection of Disease/Condition

So not every disease and condition is suited for an APM. A big part of the APM for CMMI is they want to see savings. It’s all about savings. Remember we got rid of the SGR. It’s about savings, and it’s about putting the provider at bidirectional risk meaning you can make more money if you do things really well, value—value is outcomes divided by cost, or you can get your clock cleaned if you don’t do it well. You actually can end up losing more money than you had bargained for.

So the characteristics for an APM consideration: treatment costs are meaningful for the payers, and in this specific case, this is CMMI. Numerous treatment options and/or an evolving clinical paradigm. We chose to look at the notion of newly diagnosed patients receiving active surveillance versus active intervention, and treatment variability in clinical practice, which there clearly is lots of variability with intra-practice, inter-practice, intra-, inter-region. Net cost savings if the variability narrowed, and would treatment sequencing be changed. And be able to define quality metrics and outcomes to ensure that the cost savings do not come at the expense of patient care. In other words, let’s just stop ordering tests and therapeutics, save a bunch of money. It can’t work that way. You have to demonstrate quality outcomes.

Scope of APM

So the scope. How many practices or numbers of physicians or other eligible professionals have expressed interest and willingness to participate in the model if it is approved? You have to get support from your specialty, and it has to have applicability to non-Medicare payers. How many physicians or other EPs, eligible professionals, and patients could participate in the model if it was expanded to scale?

So when we proposed ours, and we’re still in the process, it would be open and complete public exposure to the entire universe of your specialty.

Savings Estimates/Shared Savings

The portion of national episode that is reasonable to include in savings estimates, again, this is something that is very carefully reviewed, and so these are big budgetary assessments and a reasonable basis for increase in target utilization based on clinical analytics. And a lot of that clinical analytics requires population health experts, which of course requires resources and spend.

Quality Metrics

Quality metrics—how many? CMS does not provide any guidance. Zero guidance on what the metrics would be. Use existing or develop new ones? Well, there aren’t any so we are now creating these. This is a complete work in progress by multiple different specialties although right now there is, I believe, only about 5 or 6 in the entire world of medicine in the United States that have any APM approval. And this is now going several years into this process. So how do you tie quality performance targets and performance-based payment and repayment?

Pricing Methodology

Well, it’s a very big moving target, and it’s regional versus practice. There can be low-volume thresholds for receive 100% of your regional pricing, and a lot of this will vary, again, depending upon your region as we talk frequently about the heterogeneity of prostate cancer. There’s amazing heterogeneity in how we practice in different parts of the country and sometimes even within counties, and whether to allow the practices to voluntarily accept 100% of regional pricing, this is an ongoing work in progress, and it’s complicated, and so there are low-volume thresholds for applying these floors as well as upper bonuses. So you have stop-loss programming potentially. Very interesting if and when any of these things get approved for us. It brings into a whole notion for those of you who think about insurance or re-insurance methodologies to guard against stop-loss.

Episode Definition

So how do you define an episode? Well, there’s a methodology to attribute the episodes to practice. I alluded to that earlier. There’s a relationship of the APM to other APMs. The classic one right now is the oncology care model where there’s about a $165/member or per patient per month fee to basically do all of the encompassing care for the oncology care process. And a lot is being learned about that. And we actually tried to model our APM off of that with a marked reduction in that fee component.

Monitoring/Auditing

So in the monitoring and the auditing, there has to be monitoring for increased prevalence of prostate biopsy, particularly talking about our act of surveillance, act of intervention, potential APM, and there need to be monitor incentives to either start patients on active surveillance versus not, monitor incentives to keep patients on surveillance even though they should appropriately start an active treatment. And as you can imagine, surveillance, screening appropriately, and intervening or not, thinking about how you now integrate that into an economic business healthcare model has taken on its challenges. This is what we’re trying to address.

Integration and Care Coordination

So how the model would lead to greater integration of care coordination among practitioners and across settings, a completely tabula rasa blank slate moving target. To what extent would the proposed model result in changes in work force requirements compared to more traditional arrangements? Well, in order to do things well oftentimes, as we all know, it can no longer just fall on the shoulders of the clinician. There has to be a coordinated care team, and that includes advanced practice providers. That includes medical assistants. That includes all of the people who have to input in your EHR and take the time to make sure all of these things are being documented accordingly.

Health Information Technology

So HIT, the timing and frequency of data transitions from CMS to participating practices is a methodological requirement. Will any of these HIT innovations be used to support improved outcomes, improve the consumer experience, enhance the efficiency of the care delivery process? These are the questions that you get asked when we have prevented now to CMMI as well as to PTAC. Include aspects other than requiring the use of the CEHRT, which is necessary for classification as an advanced APM, and of course ECQM as well.

Patient Choice

So the patient choice. I’m hoping that most of you are able to follow a lot of this sort of arcane acronym soup/salad discussion of government health policy, but I think 99.9% of our patients are really clueless to all of this other than they see us come in now with laptops and/or scribes. How will the model impact decision-making ability of beneficiaries, and how will the model impact the right of beneficiaries to choose their own provider and site of services? Well, if you talk to most of your patients, they have no idea that this is going on, but this is what some of the discussion is that’s happening now at MEDPAC and at CMMI.

Summary

Even at our APM thing for almost two years now could never have done it without significant industry support, as well as a backbone of a project manager in the form of Integra Connect. This is an enormous process, and it continues and goes on. We actually were very fortunate to get strong support from the AUA and the AACU. So the development of an APM is difficult. It’s time consuming, and it’s very resource intensive. Once submitted, the approval process is lengthy. It’s ongoing. We don’t have a urology-specific APM in this country, and it should be clear to you why it is important for the economics that are in front of us and all other aspects of medicine. If recommended by PTAC, there’s no guarantee that CMS will adopt their recommendation, whether it was positive or negative, and there are no recommended proposals by PTAC that have been implemented to date. So why do we do it, any of us, and why at LUGPA are we doing this?

APM Development

Well, you can just add some Instant Apathy as you see here I think is a funny cartoon from Deepak. Just add whatever, whatever you want, I really don’t care, or as I said earlier, if you’re not at the table, you’re on the menu. And that’s one of the things that were really important to many of us, and frankly to the entire specialty.

What now?

Einstein, “Failure is a success in progress.”

How to cite: Gambla, Michael T. “Future Options for Urology Practice Ownership” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/Future-Options-for-Urology-Practice-Ownership/

Summary:

Michael T. Gambla, MD, explains how to navigate the landscape of hospital partnerships and purchases, private equity partnerships and transactions, and large groups consolidating for expansion in the realm of urology.

Future Options for Urology Practice Ownership – Transcript

Click on slide to expand

Future Options For Urology Practice Ownership

As Neal said, this has really become sort of an interesting time for urology, particularly the large, independent groups. It’s a time somewhat of survival, change, and that has somewhat lead to a lot of other large groups, be it equity groups, as Neal said, aggregate groups, and I’ll describe what these different types are, as well as hospitals sort of seeking opportunity within urology, and we’re going to take a look at what are some of the drivers for that, and then we’re going to take a look at each sort of entity and how they might play a role.

What’s going on out there??

So really what’s going on out there? Five years ago there wasn’t any mention of private equity in urology. We were just focused on LUGPA, independent practices, and maybe aggregating our own practices, merging the partners down the street. There was no real cash involved. It was trying to get the guy that we hated before to come join us because we needed to do a bigger project. That’s what that was about. It was about putting old legacy practices away. Now, we have all kinds of new entries into the market. So, we have hospital partnerships, somewhat what Evan was talking about, where maybe it’s a PSA agreement. We’re trying to figure out what’s the right type of a partnership there. Sometimes, it’s an outright purchase. There have been urology groups where they have been purchased by the hospital and integrated right in. And you’ve got private equity partnerships and transactions taking place. There’s been one that has already taken place, and there are a number that are on the docket for this year and into next year. They take some time to do, but we’ll explore that a little bit.

Just as a kind of FYI, the private equity investment, particularly into the independent medical practices, are occurring at an incredibly significant pace, particularly in urology, dermatology, ophthalmology and radiology. So, they know this space needs help. They know these groups have maximized their size, and so they are now coming in and saying, “How can we help you?” So, don’t be surprised if you’re running your group and you get calls, random calls, from private equity guys in New York saying, “Hey, can I talk to you about an opportunity?” Because that’s what’s happening in the space, and again you’ll see that in these multiple specialties, and I’ll show you what’s happening.

The Marketplace for Medical Groups

So, this is just a list of different transactions that have occurred. There are far more than this to list. I just thought this was a nice smattering, because it really just shows different areas. I mean, you’ve got anesthesia, USAP, that is US Anesthesia Partners. That group was a group that was purchased initially in the 100, 200 million size. It’s now over a billion dollars. It’s huge. So, these groups have increased in size. Rad Partners is a very, very large radiology partnership, and there’s just a recent transaction that took place for another partnerships that’s over 100 radiology partners. If you look through this, Schweiger Dermatology is, to my knowledge, the largest dermatology clinic throughout New York. It’s my understanding that they’ve grown in size to some 20 offices, and again, bringing in dermatologists to—and again all private equity backed, so they take the core of what we’ve built over the last 5-10 years in LUGPA, these independent groups, and then they accelerate the process. And obviously, the one in gold here is in urology, Chesapeake Urology last June, doing their transaction in private equity. Then, from this point up to now, Chesapeake has added additional groups. So, they have been accelerated, again, through the process that we’ve seen with these other types of entities, where they’re starting to grow their group beyond their initial base.

Drivers for Ownership in Urology Practice

So, what are the real drivers for this ownership in urology practice? Why do they want to come in? Well, they see the demographics. They know there’s a decreasing workforce and more increased demand. Some 10,000 people are turning 65 and going on Medicare every day, just a huge number of patients who are going to come into our arena, and they know that’s there. The young urologists, on the other hand, are looking for stability, and that stability can only come through a large group, or they go to the hospital. No one is hanging a shingle today. So, the cost of operation of doing that is far beyond what we can experience any more. So, they have to have a choice, and that choice is either the large group or hospital-based environment. We know the aging population. We talked about that.

The private equity, and even the hospital in the aggregate, or it’s these different types of entities that come into the space, they understand that there is a significant growth opportunity in exploring clinical pathways with very disease-specific development, particularly a lot of talk in this conference about CRPC, metastatic disease, the new drugs that are coming through, what is the best opportunity. Well there’s also financial basis behind all of that, and so they understand that. And they know this business is not well explored, so a lot of these disease states have not been fully baked out to where programs are, as Evan was alluding, with the stents where all the group follows one pathway, and that process, when driven the right way, can create economic gain for the group, obviously for the investor, but it also can be good for the patient. So, they do look for synergy. It’s not just financially based motives. They really want to create a product, if you will, that benefits patient care because they are not going to, as Evan alluded to in his talk, there’s quality measures that are out there, and so if you’re not hitting quality measures, it doesn’t matter if you can make money or not, because eventually that will be gone.

Other opportunities—I see they want to accelerate the ancillaries, they see new growth in male and female sexual medicine, which has not really been well explored in urology. It is now becoming more explored. So, that is a new opportunity, and truthfully, having talked to multiple different types of groups that come into urology, looking for some kind of partnership, the truth is they think that urologists have always shown a predilection for large group formation. And we as a generalized group through LUGPA have kind of formed the sense that independence is what we have been seeking. And so, they’re going to try and preserve it.

Drivers for Sale/Partner in Urology Practice

So, what are the real drivers for us as urologists in a group practice to sell? Why would we want to do this? We’ve built these great establishments. We’ve come up with our pathways. Why do we want another partner? And we always know the other partner is the unknown partner. We don’t know what they’re going to do. For most of us, it was fear of the hospital partner and how they’re going to react. Now, we may have a financial partner, but the truth is these practices have become very complex micro cap businesses, 50 million, 80 million, 100 million dollars of revenue, and the truth is we’re running it with a number of urologists, guys who may never have an MBA, have never been trained in business, and now we have this monster of a machine, and maybe it’s not being run so well. So, the problem is, we start getting into different issues like increased overhead, and how do we manage that? More compliance and regulatory issues are coming up. We had to hire a security officer, a compliance officer. That’s all non-producing personnel on the list that increases your overhead, but it’s a necessity when you get to a certain size, because you become more visible to everybody.

A lot of increased IT cost. It’s far more complex. The platforms are narrowing down as to what you can choose for EMR, whether you’re going to go to Epic, or Serner, or Athena. I mean, these are big, expensive platforms to implement. Carrying cost on drugs, supplies, equipment, we know that if your IMRT machine breaks down, that’s a huge cost. Our CT broke down, and it was an uncovered cost, $50,000 right to the group, just right to the bottom line. Even though we have a contracted agreement, that particular agreement was an electrical issue. The doctors just ate it, that was it.

The billing process, think about it, now we have pre-certs for everything, and for every drug, particularly in the space we’re talking about at this conference. These are expensive drugs. Each one has to be thoroughly—go through a pre-cert process to make sure that the payment is going to be there, because we can’t afford to take the hit, which is actually why, early on in this particular arena, a lot of these drugs didn’t get a lot of momentum. There was a lot of concern whether the groups could afford to do this.

And then, finally perhaps the biggest issue I have seen, is the skilled personnel. We’re building very, very large companies, corporations, however you want to call it. Do we have the right personnel at the top, a real CEO who understands our business, a CFO, a chief information officer? Do we have a data analyst? To be able to succeed in the new environment that’s being created for us by the government we need to have these types of people running these businesses. Doing it the old way we’ve always done it won’t survive.

One of the interesting things I’ve learned, having grown my group for seven years, is that physicians don’t typically reinvest in growth. Right? At the end of the year there’s not this, hey, let’s put 20% back in the pot and build this new center. No, it’s where’s my check? Did I get paid? Where’s my bonus? How come it didn’t come? You said the fifth. It’s not here. The phone calls come in. So, the truth is, we don’t typically, as surgeons and as urologists, think about, hey, how do we grow the business here? That’s not our mindset, and you know what we’re focused on medicine, we’re focused on better care, and that’s what we should be doing, which is why we need skilled personnel.

Drivers For Sale/Partner In Urology Practice #2

The other issue is we don’t have time. Most physicians at least in leadership roles are spending an increased amount of time in administration, and that takes away from good patient care and from them thinking about what’s right for patients down the stretch, or looking at new alternatives in the medical space and device space so that we can have improved outcomes. The businesses are complex, as I showed you on that prior, and then the decrease in quality of life work balance. I mean, you look at the young guys coming out, and they want to go to the hospital. They figure, at the hospital, they’ll see 25 patients a day, they’re out of there by four, they’re not going to have the responsibility of any administrative things at all, and they’re okay just taking a salary. We’ve tried to hire a number of candidates this year. It’s very difficult to compete with the hospitals. They get very large salaries up front. They get enticed by that, and they get subject to some RVU bonus, which, by the way, is subject to the hospital. One year it might be $50 an RVU. The next year it could be 45. It just depends on what they want to do. So, you’re completely subject to a hospital ruling. But, you look at this, and you think, wow, otherwise you’re running all of this. So, they get away from all that, and these are the issues we face.

Goals of Partnership: Hospital

So let’s go over some of these different entities. Goal of partnership of the hospital—in the hospital, let’s start on the physician side. It’s really a one-time sale of your practice. Right? You sell it, and you become employed. Typically, they will give you a three to five-year contract, so you have some stability. There’s minimal admin responsibility, maybe one person kind of gets elected to be sort of the chair of urology or the admin person for the group that gets pulled in. The hospital may already have a number of urologists, and they’re seeking a little bit more leadership there, and then it’s a fix salary and RVU bonus, and a lot of guys are comfortable with that. They just want to know, “I’m making X amount this year and for the next five years.” What’s the down side? Absolute loss of control. You are completely subject to whatever the hospital says. No growth strategy. Hospitals typically don’t grow urology markets. That’s not their basis. It’s not their focus, and we make a small percent of what the hospital does. So to Evan‘s point, they may worry about catheter associated UTIs and hospital-based things that they’re going to get dinged for, but they’re not necessarily looking to add the next new innovative device to urology and again a fixed salary. So, you really don’t have a lot of up side growth if a new entity comes, or a new technology comes that could potentially produce revenue.

The hospital is all about network and regional control. They can give you patient volume, and that’s what they want. And you bring that to them when you sell. It decreases the competition. You’re not fighting the hospital. You’ve joined them. They will drive their hospital plan or health plan if they have it, and to some extent because they are usually contracted with everything, you don’t have to worry about contracting, so for them this is an easy goal. They can make more money off of you. It’s increased revenue. You’re a fixed cost to them. They know how much they are going to pay you for the most part. They know what the average urologist makes. If you happen to be a big worker bee, they make money off of that. So they know that is part of the deal for them.

Finally, they are going to maximize every dollar they can make off you through their hospital outpatient surgical centers, where they get a better rate than you would in your surgical center. They know the ancillary reimbursement through a hospital contract is far better than you and I can get in our large practices, so they have a definite up side, and they know, as Evan mentioned in his, they know their margins. They know exactly how much they are going to probably make off of every single person they bring in. So, there’s an absolute win for them in doing this.

Now, let’s talk about what’s a physician aggregator. Physician aggregators are companies like McKesson, 21st Century. These are groups that are not necessarily medically based, in that they manage groups, but they’ve had other entities that they’ve come up through the ranks with that then allow groups to come in. So, in McKesson’s case, they do pharmaceuticals, but they’ve realized they could build a group around that. And guess what that’s US Oncology, over 1000 oncologists. Of course, they get all of their distribution through McKesson. So, there was a very synergistic play there. 21st Century had a very similar model. The urologists were building radiation therapy machines. 21st Century was there with their model of how they do the radiation oncology. The synergy comes together. So, it wasn’t necessarily based on sort of private equity financial motive. It was more because there was synergy.

Goals of partnership:  Physician Aggregator

If you look at this in this case, the physician—typically these joint ventures, it’s 51% sale of the practice, or perhaps just sale of your ancillary. You may not sell the practice, but you immediately sell off your ancillaries to them in some sale. Typically, it’s a little bit more blended. It will be a salary, but there will be a growth model, because they want to growth the business. It’s some blended clinical administrative duties. They don’t necessarily want to take over the entire operations of the practice. They want you to be a participant, because it’s a 50/50 type model. Typically, they will take away all of the back office responsibilities. That will not be on you any longer. They want to manage it better than you do. That is the crux of that, how it works. You’ll have influence on your practice direction, but not completely. You’ve given up some control, and so they will ask for opinions, and they’ll see if it works out. They may or may not—a great example of that is just—we have McKesson as a partner for our radiation therapy services. We wanted to institute Xofigo. They looked at it. We thought it was great. Clinically, it made sense. We thought it was great for patients. They didn’t want to be a part of it. So, we had to do it on our own, even though we have a joint venture with them on our radiation therapy, we had to build our own Xofigo lab. So, you can have little disagreements like that along the way.

It’s definitely going to be more of a corporate environment. For them, they want to build very large group design. They are not interested in 30-man and 50-man groups. They’re interested in building 200, 800, very, very large groups. That’s how they typically work, because that’s where the benefit comes to them. They want to drive the operations lower. There’s some administrative fees along with that so they can collect a little bit of revenue. They’ll control your spending, and so that’s where they’ll make some money, and typically they will try to get better contracting through their products and services. Again, they’re usually these big behemoths that can come in and have very, very large leverage.

Goals of Partnership: Private Equity

All right so let’s talk about private equity. That’s probably the closest thing to trying to keep your practice independent. So, for the physician, it’s the sale of the practice based on a number. So, typically, you’ll take a decline in your salary. So, let’s say you were to decrease your salary by $100,000, and the multiple you get is 10, you get a million dollars, but next year your salary is minus $100,000. So, if you were making 300, you’re now making 200. Then, the hope is that through their efforts, financially and management wise, you’ll grow the business, and obviously through growth of the business, you’ll recapture that as part of your income. They are very much aligned with you, as they don’t take any money off the table until they sell the company. So, there is no management fee. They don’t have any kind of administrative fees. You manage your practice alongside with them. You keep your board. You keep everything as far as controlling. They’ll interject where appropriate. They’ll help you do pro formas. They’ll help you do management, but they don’t get any money until they sell the company.

Now, there will be a sale of the company, so you have to understand your company will be sold from one firm to another firm five years later, and you may not know who that partner is. And the truth is, unless you put it in a contract, it could be a hospital, it could be an aggregator, so you have to be careful about when you’re doing contracting, what you will agree to for that second bite. However, when you do that second bite, you will also get another large distribution. So, because you’ve grown the company and the company will be sold at a certain multiple, you’ll also benefit from that. So this type of model has the opportunity to give you income or what we’ll call take some money off the table, but you have to be ready to engage, and this is a very grueling process in getting this done. On the private equity side, they want a platform or an add-on practice. We’ll describe what those are in a minute. They will explain their ancillary services, ASC, imaging, etc. They are going to do a practice management analysis improvement. They’re going to do a business operation data analytics. They’re going to come in, and they’re going to look at your operation. And they’re going to refine most part of it because the truth is we don’t manage them all that well. So they’re going to find ways to tweak things, and basically they know there’s a lot of margin left on the table that we don’t really capture, and they are going to capture that for you. Again, depending on the type of ownership you have with them, you will benefit in that up side. So a lot of times you will benefit in how they save you money, because they have to be aligned. If you’re not working, they’re not making.

They’ll consolidate any redundant services, and then again, you’ll sell your practice within a time frame of three to five years. That’s usually what it takes to turn these—I don’t want to say turn the groups around, but to refine them and get them ready for sale. I will say, however, they also will engage in new therapies. So, if they see a therapy that is the opportunity to improve patient care and have a financial reward associated with it, they’re going to promote that. So, if you weren’t going to capitalize something that you really wanted to do because the physicians have to capitalize it themselves, this is an opportunity to do things like that.

Who are you?

Who are you? Platform groups are large groups. They have everything intact. They’re very well-oiled machines. They’re typically the size of 25, 30-man groups. They have geographic presence. They’re culturally integrated. They function as one group. Add-ons, much smaller groups, typically an office manager. A lot of services are outsourced. They may have some ancillaries. They don’t have the total presence in the area. So, most private equity groups will start with a platform group and then bring add-ons or bolt-ons. What are the four basic objectives for private equity to invest?

4 Basic Objectives for PE to Invest in Urology Groups

They want to do a consolidation. They want to have diversification so they want to expand you so that if one area or market goes down the other area can be supported. They want to unlock all of the potential of your ancillary services, and they want to make sure that the administrative services, the back office operations are consolidated efficient and best practice.

Before you sell…maximize the opportunity

So, before you sell, maximize your opportunity. So, if you decide to engage in this process, which I have been through and still continue to feel like I’m going through, you need to understand that this is a very long process. It is typically a 6 to 12-month process to do this. You have to have strong physician leadership, and you have to have strong group leadership where they believe that you’re going in the right direction. As Evan said, herding cats can be difficult for getting them on a stent. Herding cats for this is a long, enduring process. You really have to be motivated to say this is where we want to go. The legacy practices that you’ve had when you all combine have to go away. They won’t tolerate cultural lack of integration. You have to have a defined organization chart within your system as to how the CEO operates, and the COO, and everyone underneath the managers. You have to know your financials inside and out, because they’re going to know your financials inside and out. Create flexible governance, and understand governance really well, because they’re going to ask for it. They’re going to want to know how your board manages things, who manages things, who’s appointed in this area or that area for committees.

Typically, they are going to want the entire group on one compensation formula. That may be what some groups do right now, other groups tend to have multiple different compensation formulas. That makes it difficult for them to understand, and so they will bring you to one. And they really want you to one, and they really want you to think like an investor. So when you’re aligned with a private equity group, you are an investor in your own company. So if you invest in Coke, you don’t drink Pepsi, and that’s how they see it. So, if you are going to invest in this group, they expect that you are going to do everything for this group and that you’re not going to take patients to some outside surgical center because that goes against their model. So, you really have to think like an investor.

And obviously they want you to build equity in the practice because they are aligned with you. They want to build it alongside.

R. Jonathan Henderson, MD, presented “The LUGPA Alternative Payment Model (APM) on Newly Diagnosed PCa and the Role of Active Surveillance” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado.

How to cite: Henderson, R. Jonathan “The LUGPA Alternative Payment Model (APM) on Newly Diagnosed PCa and the Role of Active Surveillance” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/The-LUGPA-Alternative-Payment-Model/

Summary:

R. Jonathan Henderson, MD, summarizes the Large Urology Group Practice Association’s (LUGPA’s) efforts to develop an alternative payment model (APM) for urologists treating newly diagnosed prostate cancer patients. He explains the roadblocks to reaching this goal, including conflicts with the Physician-Focused Payment Model Technical Advisory Committee (PTAC).

The LUGPA Alternative Payment Model (APM) on Newly Diagnosed PCa and the Role of Active Surveillance – Transcript

Click on slide to expand

Disclosures

By way of disclosures, the top bullet are my disclosures. I have a speaking arrangement or consulting agreement with those companies, and this project itself was funded by LUGPA, Myriad Genetics, and Integra Connect. I want to thank Drs. Cooperberg, Davis, Penson, and Stimson, who are not LUGPA members, but helped tremendously in this project, and the statistical work and actuarial analysis was done by Milliman and Associates.

LUGPA APM Overview

The overview, you know, MACRA—and Dr. Shore explained this process a couple of days ago, but MACRA established two main paths for payment in the United States going forward, MIPS, merit-based incentive payment system, which is continued fee for service medicine, with some supposed quality measures put in. And then alternative payment model, which included two-sided risk where you basically have to say, look, if we’re putting, if we’re doing better quality medicine, we want to share in the savings that we’re providing, so you are basically putting your money where your mouth is. This past month though CMS followed up on MIPS, which they have watered down consistently over the past two years, and they have watered it down to the point where MIPS is basically no change from the past fee for service that we have lived under for the past 20 years. To qualify for an APM, you have to have 20% of your Medicare patients eligible and participating or 25% of your Medicare dollars at risk in that goal.

So Deepak Kapoor and I sat back, and we thought about it. What would be the easiest way to create an APM that would allow our groups to qualify and it seemed that prostate cancer would be the one code that universally would be most likely to capture 20% of our patients or 25% of our dollars.

Principals

So the principals, and my apologies to IMP that got transliterated there, but Dr. Kapoor’s group, IMP in New York is a large group, over 100 physicians, large metropolitan area, and they have ancillary services. My group in Shreveport, Louisiana has about 20 physicians, a small city and ancillary services, and after we started the project, we realized that we really need to look at somebody to make this attractive to all urologists who doesn’t have ancillary services, so we got with Todd Cohen‘s group in Charlotte, NC, which is 40 physicians, but they are a CON, a certificate of need state, so they own no ancillary services, and that actually proved well when we got to talking with CMS.

LUGPA APM Overview #2

So, in overview of the background, we know that approximately 79,000 Medicare beneficiaries are diagnosed with prostate cancer each year, and about 63,000 of those are localized prostate cancer. We also have to recognize the historical fee for service does not align with current best practice standards. It doesn’t—well, it proves itself out in the fact that 77% of the patients receive active intervention. So, we proposed a physician-focused payment model that is episode-based payment for low-risk prostate cancer. It aligns financial incentives with clinical best practices, and most importantly shared decision making with the patient, qualifies under statute as an advanced APM. We submitted a letter of intent, which was accepted by PTAC. So you’ve got CMS, runs all of Medicare, and under CMS is CMMI, the Centers for Medicare and Medicaid Innovation, which runs these new projects. And under CMMI is the PTAC, the Physician’s Technical Advisory Committee that has to approve these new APMs. So, they accepted a letter of intent and the proposal was accepted in July.

LUGPA APM Overview #3

Then we went to Maryland and met with CMMI in July, had a lot of questions and answers, about two-hour session, was really good. They gave us some things we needed to work on. Went back to the drawing board, then submitted with the updates. It was reviewed by the PRT. Again, everything with the government is alphabet soup, right? The PRT is the preliminary review team, which is a subsidiary of PTAC. So the PRT reviewed it in October, had a few more suggestions, and questions back to the drawing board again, final proposal submitted and reviewed by PTAC this last month, and I will give you an update later on.

LUGPA APM Overview #4

So what this APM did, is it is—the episodes were attributed to urology practices. Dr. Shore went over the attribution process a couple of days ago, pretty complex and sort of silly, but in our APM, we guarantee that when you have a patient diagnosed at your institution with a prostate cancer, everything thereafter gets attributed to you because the total 12-month cost of care is attributed to you. I’ll go into why that matters a little bit later.

It is a two-part payment model. So once you have a patient who enters active surveillance, you receive a $75/month care coordination fee, and at the end of a 12-month period, there is a performance-based payment that basically the savings you have performed for the system in coordination with the quality metrics you have to hit gets shared between you and CMS.

So, the quality measures I’ll go into later include efficiency and cost reduction, communication and coordination, outcomes measurement and process. We use the oncology care model as a basis for our foundation, really, because it is one of the few APMs that’s been approved. It seems to work well for medical oncologists.

Beneficiary Population

So, the population, again, 63,000 of the Medicare beneficiaries have localized prostate cancer. Only 23% in 2015 received active surveillance, and there is a huge variation across regions. If you look at the Medicare regions across the country, the variation active surveillance uptake went from about 19% to 25%, but if you drill down deeper into a county or metropolitan area level, that variation was from 10% to 70% utilization of active surveillance across the country. So, there’s a huge variation. We know it’s under utilized, and research shows that about 43% of localized prostate cancer has a Gleason 6. So, they should be candidates, and what we wanted to do was align the financial and quality incentives to increase utilization of active surveillance.

And we have to admit that the USPSTF recommendation was in part spurred by the fact that we weren’t utilizing active surveillance enough.

Proposed Episode Definition

So, the proposed definition for an episode is a 12-month period that begins the date of the diagnosis of prostate cancer. The patient then is attributed to that practice. I’ll show the active interventions on the next slide. Active surveillance is defined as no active intervention 12 months after a biopsy. So, it’s very simple, and the really nice thing is you don’t really have to do anything at the group level, because Medicare tracks all of this from the claims data that is already being submitted. So, the subsequent episodes for the beneficiaries, for 12 months you get the care management fee, and that care management fee is not included in the total cost.

Estimated National Episode Volume & Cost

So, as you can see, active surveillance patients are then stratified by how sick they are into tertiles, and the active intervention basically is everything that you can think of goes into that bucket.

Estimated National Episode Volume & Cost #2

So, active intervention spending is $20,000 per-patient per-year higher than active surveillance in the initial 12 months. For those patients who would have received a prostatectomy, staying on active surveillance saves about $9,000 a year. For those who would have received radiation therapy, surveillance saves about $23,000 a year. And so, our model shows about a 250 million dollar savings per year for Medicare.

Care Management Fee

The care management fee, again, it’s $75 per-patient per-month. The rationale for that is active surveillance. Retention is very low. There’s a number of reasons for that, and so, what does this fee encourage? It encourages the provider to spend more time on beneficiary compliance with appointments, on education about disease progression, lab coordination, and most importantly, shared decision making with the patient, social service coordination, and then care revision, the plan revision, and review monthly.

Performance-Based Payment

In addition to that monthly payment, we’re looking at a retrospective comparison of the actual spending episode over that 12-month period, along with a target price, and that target price is set across all initial episodes of practice based on your historical cost of care for that patient, and it blends your practice specific cost with the region’s cost. Low-volume practices who couldn’t have a statistically meaningful individual price set would be given 100% of the regional goal. So again, that is based on three years of historical data. To back up a little bit, when we started this project, we did a three-year retrospective chart review to look at cost analysis. We then convened a panel of experts and made an algorithm for active surveillance and did a prospective, six-month period using that algorithm to determine what practice cost would be.

So, we intend to align incentives to utilize active surveillance. We incorporate the historical prevalence of active surveillance at that practice and blend that with the regional. That gives us a target that we are, again, the shared performance-based payment after 12 months is going to be distributed on quality, and the delta of your historical active surveillance rate, along with your new active surveillance rate.

Performance-Based Payment #2

So, if your actual spending over that 12-month period is less than the target, your practice gets to keep up to 100% of the difference based on quality performance. If the actual spending is greater than the target price if you are more expensive than you should be, your practice is going to have to give money back to the system, up to 125% of the difference, again, based on quality measures. I’ll get to that in a minute. What’s important, though, is off the top, CMS takes 2% of the target price. Why that is important is CMS is guaranteed by that to save money. There’s some Stark law implications that have to be changed, and we won’t get into those weeds.

Quality Measures

So, the quality measures that we propose, number one on efficiency and cost reduction- there already exists a quality measure for the avoidance of over use of bone scans in low-risk prostate cancer. Communication care coordination- there already exists a code for biopsy follow-up with the patient outcomes is a new code. So, time on active surveillance- we would create a new G-code that would report that as a quality measure, basically how well are you doing keeping a patient on active surveillance, and then process, which is a shared decision making code, which is modified from an existing NQF code.

Time on Active Surveillance Quality Measure

So, time on active surveillance quality measure. Active surveillance is easily measured in claims data by no active intervention in a 12-month period. The G code is filed when a patient leaves active surveillance based on that patient’s choice, based on your determination that he is non-compliant or his disease has progressed. Again, no extra filling is needed. It’s calculated from claims data.

Shared Decision Making Quality Measure

So, the shared decision making quality measure is modified from 2962, and basically the patient just answers a questionnaire that says, “Did the provider describe the options between intervention or surveillance? Did he discuss the reasons for intervention or the reasons for surveillance? And most importantly, did the patient perceive that he was involved in that decision making process?”

So What Happened?

So what happened when we got to PRT? The preliminary review team voted against approval, but it still went forward to PTAC. After they vote against approval, we already had letters of support from the AUA and the AACU, but we then got some physician experts around the country help write letters of support. And also, the patient advocacy groups PHEN, ZERO, and PCEC also wrote letters of support. Nevertheless, we got to PTAC, and Dr. Shore and Kapoor presented the proposal there, they still voted 8:3 against approving the measure stating that it only met 8 of the 10 criteria, which is, I have to point out, far better than any other proposal thus far has gotten from that committee. They pointed out that ours is by far the best proposal they have received since MACRA passed. They disagreed in the 2 out of 10 criteria based on payment methodology. They did not like, philosophically, the fact that we would be attributed the total cost of care in that 12-month period. And care coordination, they did not like the fact that, per-patient per-month fee, we didn’t have an outline that showed a formula, basically, how everybody else who participated in the care of that patient would receive a portion of that fee. Basically, if you’ve got internists, how much are you going to share with them with that $75/month, and if you think about it, we couldn’t put a formula in there, because there is no way to formulate every locality in the country, and how they should distribute that. It should be left open.

PRT Comment

In their comments, it’s a little telling here, they said the majority of the PRT thought the proposal technically satisfied many of the high priority payment model criteria. The PRT members all do believe this proposal would align incentives more in the direction of the evolving standard of care, but we also unanimously felt the net effect of this proposal is wholly unsatisfactory in the signal its favorable recommendation would send to other applicants and specialties. So, in other words, make an example out of us. The PTAC process is unlikely to serve the secretary, the Medicare program, or the Country well if it comes to be seen as a device to be paid more for providing guideline-recommended care for patients. And at this point, we did a little AFLAC duck thing? Huh? Because that is what MACRA said you are supposed to do.

More PRT comment

Further comments from PRT, “It is difficult to estimate how long the transition to active surveillance for appropriate patients would take under the current payment system, as the shift requires changing behavioral patterns within a specialty.” Huh? That’s exactly what we’re trying to do.

Kapoor

So Dr. Kapoor summed it up very well, “Although the PTAC did not recommend the proposal, they acknowledged that it met the criteria for adoption as an APM, that it would improve patient care, that it would save program dollars, and it would reduce disparity in access to services. Fundamentally, their rationale was not on the quality of the proposal, but rather one of philosophy. The PTAC’s grounds was that it was inappropriate for specialists to benefit from a total cost of care model where payments were aligned with quality outcomes. All of us, as well as Congress and CMS disagree with that view.” Again, basically this proposal did exactly what Congress said we should do when they passed MACRA.

Conclusion

So, in conclusion, the triple aim set forth in MACRA was met by our proposal. The LUGPA APM qualified as an advanced APM, which going back to Dr. Shore’s talk the other day, is the highest tier of APMs and allows the practices to benefit the most, and the LUGPA APM, as we know from nationwide surveys, appeals to many urologists both in large and small practices, independent or hospital owned, and in practices with or without integrated services. It’s a substantial value for CMS, and as I pointed out, a substantial savings for the country.

Appendix Slides

The rest of the story is that we’re not done yet. We’re still in process. We’re fine-tuning the proposal, and we’ll take it back to CMS later this year. So thank you very much for your attention.

Practice Increases AS from 23% to 33%

Comment from Dr. Raoul S. Concepcion:

I congratulate you on really distilling this down, and I just want the audience to be aware that this is a very long, arduous, and expensive project. Submitting these APMs requires a lot of man hours and a lot of dollars, and I think what is really egregious about the PTAC recommendations and their statements is that the modeling that was used with this care fee of $75 is exactly how the OCM was modeled, which is $160 a month, and PTAC makes the ridiculous statement why should urologists be rewarded for doing the right thing, acknowledging that active surveillance is appropriate therapy, but that is exactly what they are doing to medical oncologists.

Practice Increases AS from 23% to 25%

Comment from Dr. Thomas Keane:

Urologists, I think, traditionally are known as some of the smarter business people that exist, and LUGPA is perhaps one of the smarter of all of the groups within urology, and I would say these guys are terrified of that proposal, because what it is going to do is set the path for all of the other specialties to follow, and it’s not so much what you guys are putting together, which having listened to it, is completely along the lines of what they wanted. It’s rather terror of what happens if the entire medical community comes onto it, and everybody starts saying, well, we want the same for congestive heart failure, we want the same for stroke patients. Somebody has looked at that and said, oh, this is—we never thought they would be able to do that, and you are. And I think it is a whole new concept for them, and they are probably scared.

How to cite: Lewis, Tamra. “The Role of the Young Urologist – What Makes Millennials Tick?” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/The-Role-of-the-Young-Urologist/

Summary:

Tamra E. Lewis, MD, FACS, defines the term “millennial,” discusses urology practice demographics and work culture trends, and talks about how to recruit and retain young urologists in independent practices. She explains how these shifting attitudes and trends led to the founding of the Young Large Urology Group Practice Association (LUGPA) organization.

The Role of the Young Urologist – What Makes Millennials Tick?

Click on slide to expand

The Role of the Young Urologist:  What Makes Millennials Tick?

So, I was tasked with discussing the role of the young urologist or the Millennial urologist.

Disclosures

These are my disclosures. None are relevant.

Objectives

My objectives, so first define what a Millennial is, who the Millennials are as a group, how that fits with the practice of urology, and then talk about future leadership.

What is the Millennial Generation?

William Strauss and Neill have described a theory of recurring generation cycles in American History. A social generation is made up of a group of people born over a span of roughly 20 years, or about the length of one stage of life, childhood, young adulthood, midlife, et cetera. Generation is defined by three characteristics. There’s age location in history, i.e. they’ll encounter key historic events at roughly the same stage of their life, they share common beliefs and behaviors and they have a perceived membership in that group.

What is a Millennial?

So the Millennial generation applies to individuals who are coming into adulthood at the turn of the century, so born between about 1980 to 2005 which would make them roughly 18 to 35 years old today. Prior generations would be Generation X, the baby boomers, the silent generation and then prior generations would be the GI generation, lost generation according to Ernest Hemingway or the lost generation, the greatest generation according to Tom Brokow. Today 32% of US adults are Millennials. They surpassed the baby boomers in 2016 as the largest population group, 75 to 80 million Americans are expected to make up 50% of the US workforce by 2020.

Millennial Traits

So, traits attributed to Millennials by Strauss and Howe include special, sheltered, confident, team oriented, pressured and achieving and these are based on a historical repeating cycle and based on the cycle, they predicted the Millennials would share traits with the civic minded GI generation. Personality surveys of Millennials identified traits of confidence and tolerance, but also entitlement and narcissism.

Millennial Traits and Attitudes

So, this may hold some selection bias as the Millennials assess tend to be white, affluent teenagers who accomplish great things as they grow up in the suburbs, who confront anxiety when applying to super selective colleges, and who multitask with ease as their helicopter parents hover reassuring above them. This may not accurately reflect other socioeconomic groups. A Pew Research Poll in 2015 found that the majority of Millennials actually did not like the Millennial label.

Millennial Traits

Time Magazine ran a cover story in 2013 called “Millennials: The Me Me Me Generation” that put a slightly more positive spin. The advances in technology have empowered individuals by giving them the resources to compete against larger organizations, think hackers versus corporations, YouTube creators versus traditional studies, app makers versus entire industries. Millennials may not always respect authority. It’s not that they resent or rebel against it, they just don’t always feel that they need the institution. To them, the world is more flat in terms of hierarchy. They are optimistic. They can be entrepreneurial. They are better informed and they are willing to challenge convention to find a better way to do things.

Millennials are the Most Ethnically Diverse Generation

They are the more ethnically diverse generation.

What Characteristics Define a Millennial?

They grew up in an electronic filled, online, socially networked world. They have been exposed to diverse array of marketing techniques and tend to be much more skeptical of them. Social media and sharing, or sometimes over sharing, of information is natural and, as I showed before, they are more ethnically diverse, and therefore likely more tolerant of difference.

Workplace Attitudes

So, workplace attitudes. Baby boomers value loyalty, work ethic, a steady career path and compensation. Generation X, there’s a transition to an improved work life balance with a heightened focus on individual advancement, stability and job satisfaction. The Millennials shows emphasis on producing meaningful work, finding a creative outlet, and have a preference for immediate feedback. They introduce, introduction of social media has augmented some collaborative skills and create a preference for a team oriented environment.

Millennials in the Workplace

Millennials expect free flow of information and have a strong connection to their supervisors and like frequent feedback. They are more likely to seek aid or benefit from their advisors or mentors and this creates a more flat work environment. They do expect more of a balance of personal and professional life, and there is a greater divide between the baby boomers for a more work-centric generation, and the subsequent two generations. There’s a shift towards public service, emphasis on volunteering and social responsibility, but we also have the idea in school and sports that everybody gets a trophy, and so this may lead to unrealistic expectations in the workplace.

Understanding Millennials

Being raised in an environment of constant praise and reinforcement, they expect that to continue in their adult life. So, understanding Millennials create an atmosphere of inclusiveness through transparency and ongoing dialogue. They expect transparency in the consumer workplace and they are expecting it in medicine as well. There’s a willingness to question authority. Generation Why. They want to be part of something, have a voice and be heard. They would rather help solve the problem than be told the solution.

AUA Census Data

So, here’s that pie graph that kind of shows that. According to the most recent AUA Census Data, there are just over 12,000 practicing urologists in 2016. Females make up 8.5% of the urologists in practice, but under the age of 45, almost 20% of urologists are female.

Young Urologists with Fellowship Training

More young urologists have fellowship training than the previous generations.

Work Setting by Gender

And, if we look at practice demographics by gender, females are more like go into academics and less likely to join independent urology groups.

Young urologists are less likely to be in private practice than prior generations

So, it’s similar to last night. There are fewer young urologists overall going into independent private practice, and I kind of pointed this out earlier, than the previous generations. Why is that? Do they prefer employment? They want a guaranteed salary? Is loan repayment an issue? Are they less entrepreneurial, or is it just a lack of exposure to private practice and business training?

Young Urologists in Private Practice

So, if you look at Millennial urologists, females especially are much more likely to be employed physicians.

Technology in Medicine

So, what changes do we see as the Millennials enter the urologic world? There’s a greater alliance on technology. Next generations are accustomed to having information at their fingertips. When confronted with a question, they’ll just Google it rather than write it down and go look it up later, and because of this, the practice of medicine is no longer limited to the content of knowledge of the individual physician. Social medial is definitely here to stay. This is the third urology conference I’ve been to this month, and the prior two each had a talk about social media in urology. There are several websites for physician dialogue that exists as well as Facebook groups.

Recruiting Millennials

So, recruiting Millennials. How do they look for jobs? They look in the traditional platforms, hospital websites, online job posting and recruiters, but they also use social media and word of mouth, and with social media, the network is much wider. They research a lot online using a search engine, social media, rating sites (whether those are good or bad), and a lot of it they’re just going to do from their phones.

Recruiting Millennial physicians

So, they use the transparency in the consumer world and don’t know not to expect it. In the medical world, especially when it comes to things like insurance and billing, is about the least transparent industry except for maybe politics. But, it’s important to be up front about compensation and expectations. So, discussing ownership opportunities early and being clear. Be authentic. Let your true culture, people and brand show through. Also consider how do you stand out from other groups or hospital systems. What makes you different? If you don’t know, it’s a good question to ask, and if you’re not finding what you need, revisit your recruiting strategy.

Challenges in Recruiting Millennial Physicians

There are challenges in recruiting urologists, especially into independent urology practice. Student loan debt has doubled in the last 15 years, and when I talk to some current residents, I was hearing numbers more like $300,000 of student loan debt. With the change in work hour limits during residency and increasing education on burned out, as well as exposure to older physicians through training or family, Millennials want more flexibility, and this can lead to mismatch in goals. Millennials can be viewed as a bunch of lazy kids who aren’t as dedicated and don’t want to work as hard, versus, “I want a rewarding career, but I don’t want to be as overworked or burned out as you seem to be.”

From Speaking to Some Current Residents…

So, I spoke to a bunch of residents nearing graduation currently about their thoughts and these were some of the things that they had said. They are concerned with a preconceived notion of millennials and who they are. Work life balance is important, but most don’t want to be employed or a shift worker. They felt confident that they can make a good living as urologist, so money is not necessarily the first factor they consider. They view themselves as innovated. They want to bring new ideas and a fresh perspective. They are interested in utilizing technology. They want to have a voice and opportunity for a seat at the table, but they feel like they don’t understand the business of urology, especially private practice.

Retaining Millennial Urologists

Physician turnover rate’s increasing. The highest seems to be between the second and third years in practice and this can be as high as 20% in small groups. Assigning a mentor when you bring in a new physician in an extended on-boarding process of a year or more has been linked to lower turnover rates, and turnover does increase with mismatch between culture, and the individual expectations, and so, it’s important to be clear about those expectations and to give feedback regarding compensation, RVUs, quality measures, patient satisfaction and leadership opportunities can help with retention.

Why YOUNG LUGPA?

So, this is part of the drive behind young LUGPA. Our goals are to increase diversity, to attract young members, explore the needs of early career urologists, enhance the practice of young physicians, including the transition into practice, facilitate the participation of young urologists in policy development, and other activities of LUGPA, promote young physician leadership throughout the organization of LUGPA, and increase leadership opportunities for young physicians, and train them for future leadership within LUGPA within their own groups.

Young Lugpa Committee Members

So, here are our committee members.

Who are YOUNG LUGPA Members?

Who are young LUGPA members? So, they are fewer than 15 years out from fellowship and residency. They practice within LUGPA groups. We sent out some E-blasts last fall to help to try to identify some of the young members, and the last count I heard was 381 young urologists, there’s likely more out there. There are also similar efforts in other urologic organizations, the AUA young leadership program, the regional sections are starting to show some interest, and specialty societies. And, the goal of all of these is to try to identify young members, encourage them to get involved, and to provide value to them.

Integrating the next generation

Integrating the next generation. It’s important to have transparency within our organizations and to help the younger generation to understand the business of urology. Mentorship is key both within the organization and beyond, and you can help by supporting and participating in Young Urology programming. This also offers the opportunity for networking with potentially future people who might want to join your group. Leadership education is important, and I encourage you to look for opportunity to give young urologists a sit at the table.

Neal D. Shore, MD, FACS, presented “The Present and Future of LUGPA” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado.

How to cite: Shore, Neal D. “The Present and Future of LUGPA” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/The-Present-and-Future-of-LUGPA/

Summary:

Neal D. Shore, MD, FACS, summarizes how the Large Urology Group Practice Association (LUGPA) has and continues to preserve and advance the independent practice of urology by healthcare policy advocacy, business and administrative excellence, clinical and therapeutic education, and ensuring the success of future leaders through their Young LUGPA program.

The Present and Future of LUGPA – Transcript

Click on slide to expand

LUGPA 2018: The Present and Future

So I’m going to talk about LUGPA, first so many of you in the audience may be very familiar with who LUGPA is, the Large Urology Group Practice Association.

LUGPA 2018

We started literally 10 years ago, and some of the presentation is on the plenary, or the keynote, I gave at our annual meeting this year, but with some twists. So what are the challenges confronting the independent practice of urology? What will be LUGPA’s role? LUGPA now represents about 2,400 urologists, about 150 member practice in 46 states in the United States. I’m going to review for you today what we’ve accomplished, why we think we have value, in addition to so many other really important urologic associations, and what can we do to get better.

LUGPA 2018 Priorities

So our mission, what is LUGPA and why did we start? It’s to preserve and advance the independent practice of urology. And so we sort of have two essential tracks. The business and health policy—well, really three tracks, health policy and advocacy, and as everybody knows, if you are not at the table, then you’re on the menu when it comes to governmental legislation and regulatory affairs. And then, the other thing that has really changed for many of us, you know, whether you are comfortable with it or not, is the fact that we became physicians, clinicians to take care of patients and do the right thing, but the clerical burden, and the regulatory burden, and thus the ratio of business of healthcare to clinical healthcare, has changed dramatically, and so it would be imprudent not to recognize that and not to do things to optimize the ratio of business and clinical excellence.

Headwinds Abound

So, we have a lot of headwinds that abound, and so how do we work our best? You see the three people off on the right there. Sometimes, when you’re at the head of an organization, you can see yourself as being that person on the far left, if you’re not careful, to work well with your board.

Headwinds Abound

So what are some of these headwinds? Well, there’s increasing work volume, declining reimbursements. This clerical regulatory burden, there was just an op-ed piece on it in New England Journal this week. It’s creating a tremendous amount of burnout. So, how do we make sure we avoid this burnout? And we’ll talk a little bit about that. All of these health policy changes, clinical advances, how does one find the time to keep up with it? And I think the answer is- it’s a Herculean challenge.

You have to have collaboration. You have to have non-physician and physician resources in order to do it. So, this is the notion of teamwork and collaboration, and we all went to pre-med, med school, residency, and sort of this lone wolf mentality. That has to change. It’s not sustainable. Practice ownership, what is the price of independence? We’re going to have a presentation at this meeting on some of these things that are out there competitively competing, possibly threatening the independent practice of medicine, let alone urology, and that would be hospital-based institutional systems, and now private equity organizations, which are really making a strong play in healthcare.

So, we have to avoid these internecine conflicts with our fellow societies and specialties and get away from the circular firing squad, what payers like and government officials see as completely ineffective in us getting our message across, which is first and foremost, how do we do the best patient care we can do? And I think we have historically had problems with this, whether it’s how we interact with – in a multi-disciplinary way academic community, radiation oncologists, nuc med radiologists, med oncs, urologists, primary care. We have to do better.

And I’m going to talk later on today, and there’s going to be more on these federal barriers, which get promulgated without any sort of stakeholder involvement of the folks who are at the front lines, and that would be us.

So why is this important? There’s a perfect storm. We have a person/power shortage. We have a greying of the world, particularly the United States, what some have called the Silver Tsunami, generalists versus specialists, it’s not any way feasible, a sustainable option. And then there is this thing that we all talk about at dinner breaks and at coffee breaks, is how do we do this life balance, and avoid burnout, and this topic is ubiquitous in publications and on websites. It’s a real, real significant issue.

How can we trim our sails?

How do we trim our sails? How do we deal with these headwinds?

Health Policy Advocacy

Churchill

Here is Churchill. You know, I was always fond of giving Churchill quotes, but I don’t think we’re in our darkest hour. As he said, “You must put your head into the lion’s mouth if the performance is to be a success.” And we at LUGPA really feel strongly about that, especially on the health policy side, and we also on a personal level I’ve hoped to be able to champion to our colleagues the importance of recognizing that urologists can deal with systemic therapies, and that would be in all of GU oncology, not just prostate, but bladder and kidney as well.

“Success isn’t final, failure is not fatal; it is the courage to continue that counts.”

Health Care Policy

So health policy, there’s the in-office ancillary services exemption, which gives us the ability to have various services, whether it’s diagnostic imaging, in-house pathology, radiation oncology services. We’ll talk more in this program about Stark reform and how it’s quite antiquated and preventing us from doing the – and moving forward in the world of MACRA. And we’ll get into that in a lot more detail.

The USPSTF, again, a lecture prep coming up on that, and really fascinating insight into how things occur in the United States oftentimes, which we are completely obtuse regarding our awareness, but yet, how they really affect what we do and how we manage patient care. This has now been repealed, the Independent Physician Advisory Board, which had unbelievable absurd authority. Fortunately, that’s now been repealed. All of these things are policies that LUGPA spends a lot of time, energy, and resources on our consultants on the hill and that we’ve been working on.

Promoting site neutrality for physician reimbursement, so that you’re not penalized because you’re in a clinic and doing the same thing that could be done on a campus of a hospital-based system and getting half the reimbursement for that. And then, looking at various reimbursement policies and CMS constant changes, and final rules that get promoted or get stipulated every year.

And in-office dispensing services, much like our medical oncology colleagues, having the ability to have flexibility to provide beyond just using a specialty pharmacy, and we’ve been working aggressively on coming up with new clinical quality measures, which is an arcane data dictionary to make sure that we have the ability to meet MIPS criteria.

“Physicians have critically important perspectives…but I don’t hear our voices enough”

Here’s Harold Varmus, known to many of you, Nobel prize winner, and former head of NCI and NIH, who spoke at Baylor College. And he said, “Physicians have critically important perspectives, but I don’t hear our voices enough.” And this is really what lead to LUGPA getting started. We had to recognize that the independent practice of medicine, certainly urology needed a voice on the Hill.

LUGPA Resources Promoting Integrative Care

LUGPA APM: A collaborative effort

We’re promoting integrative care. It’s an ongoing collaborative effort. We have an APM that was organically developed. You’re going to hear more about this, so I’ll go through this very quickly, but it was three of our important groups in New York, North Carolina, and Louisiana, and then basically LUGPA got more involved, and you’ll hear a lot more about this, and how we’re moving forward with the first urology specific advanced alternative payment model, which will give universally urologists across the entire country potentially the flexibility to better participate, not just in the MIPS side of the MACRA, but the APM side of it.

LUGPA APM Projects

Why is this important? Because this goes right to pocketbook and goes right to your ability to sustain your models, whether you’re in academic medicine, community, etc. Here’s some of the other APM projects that we’re looking at.

LUGPA: Evolution of Priorities

So the evolution of our priorities over time, again, we’re only in our tenth year. We’re a young organization. We’re finishing our first decade, expanding our membership, which we have done year on year of the 9,000 roughly or so urologists, maybe 10 that are practicing, a quarter are within LUGPA. We think we basically are from a prescription standpoint closer to 30 to 40% of actual utilization of services. We want to ensure that there’s stability and fiduciary oversight at our organization level, and we have accomplished that, thanks very much to the support of industry, as well as our membership dues. We’ve increased our full-time capacity from one FTE to now four.

Expanding Membership Involvement

When we began in 2008, we were three committees with 11 unique individuals serving. Ten years later now, we have 17 committees and 43 unique individuals serving, and we hope to continue to expand that.

Providing Resources for Effective Management of Healthcare

So resources for effective management of healthcare.

Balance: Medicine vs. Business Healthcare

As I alluded to this earlier, I grew up and my dad was a solo practitioner of family medicine, and pretty much all he ever talked about was patient care. And he was trying to retire, but he died prematurely in 1989, and his biggest complaint to me was the bureaucracy is killing me. Like in 1989 he was saying that, but as we are all aware, this is where the seesawing effect is, and if you are not paying attention to the business of healthcare, then you are really the proverbial ostrich with the head in the sand.

Practice Management for Urology Groups: LUGPA’s Guidebook

So one of the things we did was thanks to Evan Goldfischer, he put together, he’ll be giving a presentation here at this meeting, a LUGPA guidebook, which is available to all of our members and can be purchased.

LUGPA Guidebook Table of Contents

Here are just a review of the different topics and the contents, and if you look through this and you thought to yourself five, six years ago, how many of these topics would you even be thinking about at the time? But, these are all things that are incredibly important today, and continually evolving.

Practice Management Benchmarking

Benchmarking—if you don’t know the data, if you can’t measure it, then you don’t know what you’re doing, and you can’t responsively negotiate with your payers.

Practice Management Benchmarking

It’s a big part of our initiative at LUGPA, benchmarking and level setting so that our different member practices can look across within their region, across the United States and see what they’re doing well or not doing well.

Clinical and Therapeutic Education to Optimize Care Delivery

So clinical and therapeutic education to optimize care delivery, which is really my passion.

LUGPA: Clinical Education Advancements

In addition to the health policy and the business tracks, we’ve been doing education, and we feel that we’ve been at the forefront. Oftentimes, when the community folks were giving somewhat of an afterthought to it, but let me also preface by saying it all works best if we work in harmony, academia, with industry, with government, and with community. So we began our CME programs in 2010. We have regional programming, which we try to get out to all parts of the country so our members who don’t come to our annual meeting, which is held every year in Chicago, we have worked with Reviews in Urology, our official journal, E Pub, since 2012.

We began Prostate Cancer Academy two years ago, and Bladder Cancer Academy as an offer to not just our members, but also to residents, and fellows, to specifically keep them up to date and up to speed of what’s going on with all of the changes that David showed in a really remarkable way with his introduction. And now we have the IPCU-LUGPA co-sponsorship this year. A lot of folks really enjoyed getting the opportunity to come out to a winter meeting, and then we have LUGPA Onsite, which is a new initiative for this year, where we’ll actually be bringing a full day of programming on establishing an advanced prostate cancer clinic, bladder cancer clinic, kidney cancer clinic, as well as the integrated business issues. We’ll be bringing this to our LUGPA member practices so we’re really excited about that.

2018 LUGPA Regional Meetings

Here’s just a list of the meetings. Jonathan Henderson, who will be speaking at this meeting, is chair of our programming committee and these are some of the regional meetings that will be happening this year. We change the cities. We change the venues. We’re always trying to make it as accessible as possible, and by the way so these have really been wonderfully supported by industry.

LUGPA CME Program History

This is just a list of our CME programming that we’ve done, some of the topics, and you can see where we’ve been going over the last seven years.

2017 LUGPA CME Program

This year we had a program on optimizing your GU oncology cancer clinic of excellence, and this is really where I think a lot of the sizzle is in terms of therapeutic and research development.

Prostate Cancer Academy (PCA)

Prostate Cancer Academy—we co-sponsored this with Reviews in Urology and Herb Lepor, and this has been really quite remarkable. We’ve had 50 LUGPA members come. They’re nominated to attend, and 50 urology residents and fellows. And many of the faculty who have participated in that are here today, and that has really been very rewarding, and it’s a really great opportunity to try to get the newer generation to deal with the older generation and see what’s going on in all of the advances of prostate cancer.

Bladder Cancer Academy (BCA)

We had Bladder Cancer Academy last year. We did it literally right after ASCO. We had incredible attendance. We have another program March 1-3 in St. Louis, and again, what we are trying to do is get LUGPA members, and in this one in particular we actually have medical oncology fellows come to this as well. I’ve co-chaired this with Argen Balard, NYU, so these are the types of things where we combine all of the different aspects of healthcare that we can really be transformative.

LUGPA Onsite

And so in the transformative mode- here’s the LUGPA Onsite.

LUGPA Onsite: GU Oncology (Bladder-Kidney-Prostate) Clinics of Excellence

This was really bringing, you know, the mountain to Mohammed, so to speak. But a lot of our members are so busy they can’t get out, so we’re actually bringing a full day of programming on optimizing these GU oncology cancer clinics of excellence, integrating your APPs, and also understanding other key areas of interest such as the business integration and health policy, and it’s not just on the national level, but it’s also local regional as well.

Live on Demand Educational Program

We also have additional programs that LUGPA has worked with with UroCare Live TV. Here’s just three of the first ones we did in 2017. These are live programs. We do them during lunch hour. They are archived for our members, but we actually do them live sort of in the spirit of ESPN or Crossfire or something, so that it’s unscripted, not a lot of slides, but really you know back and forth, three to five members on the panel. We did developing an APCC. We did hospital ownership, and we also did establishing a bladder cancer clinic. We just did that one a couple of months ago. I did that with Ashish Kamat and Noah Hahn.

UroCare Live

LUGPA Co-Sponsoring 2018 IPCU

So here it is, we’re sponsoring IPCU with David Crawford. It doesn’t get any better than that. We’re excited about it.

LUGPA Co-Sponsoring ICPU

Here are some of the talks you’re going to hear at this meeting that David was kind enough to let us change the agenda. We developed this partnership really in late September.

Developing Future Leaders

Future leaders- I’ll skip that for purposes of time.

You become invaluable by doing things that are not in your description

Young LUGPA –Independent Urology’s Future

This is extremely important is developing future leaders in young LUGPA. We have 400 of our membership now who have signed on to be part of young LUGPA. We’re very pleased about that, really improving not just age but all sorts of diversity, and that is essential to the growth of urology.

LUGPA: Teamwork and Dedication

None of this gets done without the teamwork and dedication of a really great board that I have the privilege of leading for now, a lot of the different management. We love to work collaboratively with AUA, AACU, and SUO, as well as all the GPOs, and none of this occurs at the LUGPA level without our industry supporters.

How to cite: Goldfischer, Evan R. “Negotiating Hospital Contracts” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/Negotiating-Hospital-Contracts/

Summary:

Evan R. Goldfischer, MD, MBA, FACS, advises urologists on how to optimally and responsibly negotiate hospital contracts under present-day Fair Market Value parameters. He describes negotiating service arrangements, clinical co-management, call coverage, and quality improvement programs.

Negotiating Hospital Contracts – Transcript

Click on slide to expand

Service Line Agreements

So, we’re going to shift from the science a little bit and talk about negotiating hospital contracts. And they come in a number of different varieties. There are professional service arrangements, there’s clinical co-management agreements, there’s call coverage, and there are quality improvement programs.

Physician Health System Alignment

And when you start to negotiate, and you approach your hospital CEO, the things you have to take into consideration are: the level of autonomy that you want, the level of clinical integration between you and your hospital, the time to implement, what sort of infrastructure and cost it’s going to be, the scale, which is one hospital or the entire system, and of payer interest.

Physician – Health System Alignment Continuum

And, you know, we’re LUGPA. We’re much more on this side of the scale. But, even if you’re an employed urologist, be it directly for the hospital or in academics, you need to work with your hospital, and you need to get paid for your expertise in what you do, because you can save the hospital a lot of money by providing the appropriate services.

Why Do Hospitals Want To Partner?

Why do hospitals even want to partner with us? Well, a lot of them are buying doctors right now, but they have no idea how to effectively manage the service line, particularly if it’s a new service line like urology. They may know how to manage hospital, emergency room doctors, cardiac surgery, things that typically hospital-based, but urology is not typically hospital based, and most hospitals don’t know how to manage it.

They’re going to reimbursed on value-based care, so it’s important that we create the value for them. There is plenty of money on the table, so it’s worthwhile for them. Obviously, they need us to take call for them, and their patients require our specialization, a sub-specialization, and it improves their ability to compete for admission, so they’ve got an efficient urology service.

Why Should We Partner With Hospitals?

Why do we want to partner with them? Well, it is better care. You know, if you got a hospital to provide 24/7, 365 PA coverage for you to handle the first hits to the floor, it reduces response time for a doctor, the patients get taken care of much faster, much more expeditiously. We want to reduce their incentive to develop internal urology departments. We want to protect our independence and our referral base. We certainly want to increase position productivity. We need to work at the level of our degree in order to generate revenue for our practice. We want to help improve OR efficiency. We can help them do that, and if a hospital is part of a large system, and you partner with them, you can be the urology group for the entire system. So it helps expand your geographic reach and improves—it gets you bigger and improves your volume.

Patient Benefit

For the patients, they get improved access to care. They get consistent application of evidence-based medicine, access to well-trained physicians, improved and consistent quality and safety.

Call Coverage & QI Service Arrangements

So let’s start with some of the low-hanging fruit: call coverage. Hospital engages a group of specialists who agree to provide detailed call coverage and other quality improvement services. Specialists from more than one practice may form an LLC to be the contracting entity and physicians in the group become the on-call panel that are responsible for setting the call coverage schedule.

Call Coverage Responsibilities

It’s usually 24/7, 365. It includes ED coverage, hospital consults, unassigned patients, unassigned ED patients, you have to adhere to mandatory response times, and obviously, you have to round on those patients and take care of them.

Call Coverage Compensation

We collect and bill for our services and we get a flat fee for coverage. And the valuation of that flat fee is the extent of burden on the physician, the likelihood of having to come in and respond to the call. Are you a small hospital, a large hospital? Are you a level-1 trauma center? Are you a level-3 trauma center? You’re not a trauma center. And the likelihood you’re going to have to provide uncompensated care, what’s the free care that your hospital gives away, or what’s your Medicaid population—restricted call, meaning if they actually want you in-house, that obviously is a higher compensation than unrestricted call when you’re from home, and they’ve got fair-market value considerations as well.

“Fair Market Value” Call Coverage Sampling – LUGPA Groups

So, here is a sampling from various parts of the country of what call is. You’re not worth as much as you think you are. That’s the bottom line. When you go into a hospital and you start to negotiate, you have to understand they’re going talk to you about fair-market value, and it does have to be at fair-market value, because there can’t appear to be an inducement that they’re trying to buy your business. Remember the olden days, 20 years old, you walked to the hospital and said, “I’m going to pull all my cases out of your hospital if you don’t pay me X amount of dollars for a chairmanship or a service line management.”

That doesn’t fly anymore. Everything has to be according to the compliance policy of the hospital, of your group, and a fair-market value. Understand this, this is key, and I learned this in one case the hard way. Fair-market value is never a number. Fair-market value is never a number. Fair-market value is always a range, and you want to know what the range is, and there a lot of different companies that do the fair-market value assessments.

There are those that are typically paid by hospitals, and there are those that are paid by doctors. So, when a hospital comes to you and gives a fair-market value number, you need to know where it came from, the company that did it, and where it lies at the spectrum. Hospitals are going to try and pay you at the 50 percentile or less. They can very easily go to the 75 percentile without going through any sort of business ethics or getting lawyers involved to see if it’s actually true fair-market value. So, you want to strive for the 75 percentile. If you can get better than that, great, but then there’s a lot more compliance issues there.

So this is a range. But in general, roughly, about $600 a day, meaning a 24-hour period for a non-trauma 250-300-bed hospital is kind of the range. If the hospital’s bigger, has trauma, you can do a little bit better. But these are the numbers, just so you kind of understand what you’re going into, because you can’t walk in and say, you know, we want $500 an hour to take call because that’s what we generate in our practice per hour. Doesn’t work.

Service Line Co-management Agreement

Service line co-management. Basic structure, they provide—a group of physicians provide medical management services. The agreement can be with a single group of physicians, or multiple groups can come together to form your own company. It includes a medical directorship, and selected physician leaders work with hospital administration to oversee and implement the co-management relationship, and the hospital pays the administrative management services an achievement of defined quality objectives.

Service Line Co-management Agreement

There are committee meetings you have to attend. You have input on financial, budgetary, and strategic matters, supply utilization, staffing and management, supply utilization, you know, if you’ve got a group of 20, 25 doctors, if one group of doctors insist that we have Boston Scientific stents and another group insists that you have Cook stents, another insists that you have Bard stents, if you get everybody to agree to use the same stent, hospitals save money. Part of that savings can come back to you—service line policies and procedures, recommendations on clinical pathways and measures, program of service line outreach activities, and quality and performance metrics.

Service Line Co-management Agreement

You are compensated, again, based on fair-market value. Usually, it’s an hourly rate, depending on the size of the hospital, the size of the service line, the amount of money going through. The hourly rate is usually between $150 and $300 an hour. You’re not worth as much as an administrator as you are a clinician. There are certain caps that are going to be established, again, because they can only pay you so much money a year, and yes, the work must actually be documented or reported regularly. Our group does it monthly.

Service Line Co-management Agreement

Quality improvement, you define what the initiatives are, and then you establish gain-sharing types of arrangements based on cost reduction, and a set pool of money is predetermined for this. The longer the relationship is in place, the harder these initiatives are. Let me give you an example. When our group first started doing this, the initiatives were very simple: sign your medical records on time, your operative notes and discharge summaries, get it done within 24 hours, and the other one was show up to the operating room on time. Don’t show up a half an hour late. That was really low-hanging fruit, and for the first two years while those were in place, we got our money.

Then we started doing it. So the bar got raised—how fast did we respond to the emergency room, how fast did we respond to consults from the hospitals. So the longer the arrangements were in place the higher the bar is going to be because you’ve already achieved certain goals and they’re going to want you to achieve more goals, so understand that.

Quality Based Payment Strategies

CMS has decreased payments to hospital-acquired infections, including retain foreign objects, certain surgical-site infections. You all know this is a zero-sum game. Some people win, and some people will lose.

Understand Where Your Hospital Falls Short

So, one of the things that hospitals are really gung-ho about right now are CAUTIs—catheter-acquired urinary tract infections. They have no idea how to stop this problem, and they don’t get paid for the CAUTIs, and it’s a metric that the government really watches. So, you can establish a committee, you can establish a protocol in the use of Foley catheters, you go out educating the nurses and the ER doctors and the hospitals that there are a lot of ways to monitor urine output. You don’t necessarily need a Foley catheter when somebody is mentally competent and able to void.

One of the simple things is just stop putting the catheters in and you’ll decrease your CAUTI rate. But, that’s one thing that’s on the table that hospitals are talking about a lot.

Patient satisfaction survey, that’s a big thing right now, both in-patient and out-patient. Your length of stay and your complication rate, hospitals use Crimson data—Crimson’s based on Texas. They get a lot of data from all the hospitals. You should be meeting with your vice-president for medical affairs of your hospital on a quarterly basis. You should find out what your Crimson data is, what they have. You should understand how it is derived, and then you should set targets to try and improve your Crimson data, length of stay, complications, et cetera. And that is a way for the hospital to pay you for improving quality measures.

And some of it is, again, educational. So what do I mean by that? When you look at length of stay, you have to understand how they derive their length of stay. And if you have one Fournier’s gangrene patient that stayed in the hospital for 60 days and got multiple operations, that is going to completely mess up your length of stay data from the hospital perspective, but they’re just looking at the overall number. So again, learning how to carve out that data is important, so that you see what your true length of stay is, and you get rid of the outliers.

Another things post-operative complications. Post-op day 1, you round on a patient who’s had a robotic prostatectomy. If the doctor writes in the chart patient has an ileus, you now have a complication. No one has an ileus in Poughkeepsie, New York post-op day 1. They have decreased bowel sounds. That is not a complication, but they do not have an ileus. So part of it is learning the system, looking at the key words that Crimson is looking for and understanding how the data is derived, and you can improve your metrics dramatically—time to seek consults on the floor of the emergency room, on-time surgical starts, again, costs of the disposals in the operating room, getting people to agree to only carry one stent, one basket, et cetera.

Research programming, I know a lot of LUPGA groups are doing research. Hospitals have cancer centers now. Cancer centers make money, but cancer centers have to have a certain number of patients per year enrolled in clinical trials. Most hospitals do not know how to manage a research program to get the clinical trials. If you are doing research and you can affiliate your program with the hospital, that is something they can pay you for. It’s good for them; it’s good for you.

How Hospitals Will Evaluate Surgeons

Hospitals are going to start evaluating surgeons based on the quality of care before, during, and after surgery. There’s going to be economic credentials. They’re going to look at three surgeons who are doing robotic prostatectomies in the hospital and they’re going to want to know why one surgeon is 25 percent more expensive than somebody else. Crimson is going live with out-patient as well as in-patient data. And again, quality is the core driver.

Negotiating A Contract

So, in order to negotiate the contract, you’ve got to know your data, and you’ve got to know their data and where they’re getting it. Go after the low-hanging fruit first, understand the finances, what the hospital is looking to save, so you can monetize the metrics, and know what percentage of the savings you can get. Do not have all-or-nothing contracts. You will lose. You know where your baseline is, you know where you’re starting from. There should be an amount of money that you get when you hit your target and then an amount of money when you hit the stretch goal, and then if you become the top decile for a certain metric, then that’s more money. So, set it up on a graduating basis.

And make sure you’re not penalized for things you cannot control. Certain things the hospital has to do and have on-time start rates, for example, in the operating room, and make sure if the anesthesiologist is late, you’re not penalized because it wasn’t an on-time start.

Lessons Learned

Trust is critical, but I’ve been at my hospital now for 20 years and I’ve seen eight CEOs. Get it in writing, that contract is so important because it has to not just survive the current CEO, it has to survive probably four or five more CEOs. Your career at a hospital is much longer than the CEO or a VPMA or a chief operating or financial officer. Everything goes in writing. Don’t just count on it as, “He’s my friend, of course he would never cheat me,” in a contract later on.

There’s got to be transparency in the goals and the numbers, agreed upon communication channels, mutual commitment and—between the two, and if there’s any discrepancy how you’re going to resolve things. And there have to be defined clear measurable targets and exit strategies for both sides if things aren’t working out.

Conclusions

Hospitals that try for quality without physician engagement will fail. Physicians understand their specialty, and we should be compensated now for achieving higher quality and lower costs, and understand if we do not work with hospitals, they will define quality for us, AKA if you’re not at the table, you’re on the menu.

Michael S. Cookson, MD, MMHC, presented “Integrating the AUA Guidelines into Your Practice” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado.

How to cite: Cookson, Michael S. “Integrating the AUA Guidelines into Your Practice” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/Integrating-the-AUA-Guidelines-into-Your-Practice/

Summary:

Michael S. Cookson, MD, MMHC, describes how urologists can use American Urological Association (AUA) guidelines to better manage metastatic castration resistant prostate cancer (mCRPC) patients. He stresses the importance of urologists serving as the primary caregiver, the multidisciplinary care model, and organized sequencing of treatments and therapeutics.

Integrating the AUA Guidelines into Your Practice – Transcript

Click on slide to expand

Integrating the AUA CRPC Guidelines into Your Practice

I would say that three-quarters of the world still isn’t getting this right and hasn’t figured out a way to manage patients with metastatic castrate resistant disease to the best of their abilities with the resources available to them.

Overview

So, my goal is just to talk to you about why urologists should be managing these patients and how to kind of incorporate that multidisciplinary care plan, think about ways to do that in your own practice, review some of the evidence-based therapeutics, try not to overlap, like I’ll not talk about bone health that much because that was covered well a little while ago.

Lesson #1

So my number one message to you is that I think urologists should be the primary caregiver for men with prostate cancer as it relates to that. This includes as they progress through those roller coaster disease spectrums that you have seen on some slides to come and many in the past.

Urologist as the Primary Caregiver

The patient may progress through his disease, but he shouldn’t have to progress through multiple providers and specialists. So, I think we provide a constant to the patient in their life. It’s a real disturbing thing when you have been seeing a patient from diagnosis through treatments, and all of the sudden you tell them you’re not going to see them any more. They know something is really wrong. I think the psychological burden of that alone is a problem. We understand the progression of their disease. We understand the management options, hopefully, of patients, as they progress through those various diseases, and we can coordinate the specialty care that they need from other specialists to treat their cancer as well as lots of ancillary help. So, that is what I’m going to try to outline.

Lesson #2

We need to establish, organize, and manage the multidisciplinary care model that incorporates available resources and works best for your healthcare environment. There is not one size that fits all. So, you have to figure out what it is that you have available to you, and how you can best make that fit.

Multidisciplinary CRPC Clinic

Now, there’s been a lot done on this multidisciplinary care, and urology is late to the table for this, really. But, due to all of the excitement around therapeutics that we have and the increased need to help manage these patients, we know that patients benefit from this, not only from their psyche, and just an overall emotional benefit, but there’s good data from other cancers where they show better outcomes related to the coordination of care, and the better management that happens when experts get together and discuss the options for these patients.

Models for Establishing a Multidisciplinary CRPC Clinic

So, this is a theoretical model that we published, but the concept is there, and you have to, again, kind of figure out how does this work for me when I go home, but the ingredients are the urologist, the medical oncologist, radiation oncology and supportive services, and those supportive services should not be underestimated. Those include navigators or assistants. They can be nurses. They can be PSR. They can be lots of things, but they have to be smart enough to know what is a patient going to need and how do we maximize the visit. Tumor Boards or discussions about what is next for the patient, and how does the patient present, what other imaging or testing does he need? Clinical trials feed right into this, and we wouldn’t have good news to spread in a couple of weeks and all of the FDA approvals came from clinical trials, and so while we’re not curing cancer we are helping people and extending the quality of their life and the extent of their life. We hope to do better in the future, and if we don’t have that coordinated care where we can identify patients for these trials, we won’t be able to move the needle forward. So, I think all those ingredients go together.

Multidisciplinary CRPC Clinic

Now, if you were a patient, you would want the one stop shop, right? All in one, you go to the large group practice, you go to the center, you go to the center, the cancer center, the hospital, you’re going to see the people that you need to see that day. You’re going to block out some time, and you’re going to get as much done in that one period as you can. That is really advantageous for the patient, but not always advantageous for the provider, so that is where that navigation and coordination of care comes in. You don’t want to be sitting in your office while they’re only seeing med onc or radiation oncology and visa versa. So, it has to be worked out so everybody stays busy and it’s an efficient way for you and the patient to be seen.

Multidisciplinary CRPC Clinic

However, we know that one size fits all doesn’t work, and there may not be that option for you available. The patient may not be able to see medical oncology, because they don’t have clinic on the same day you do, or maybe physically you’re not located in the same location. The concept though would continue in an alternative model, which could be a different day if you have to or could be same day different clinic. And I’ll just breeze through that.

Models for Establishing a Multi-Disciplinary CRPC Clinic

It doesn’t really matter. I mean, it’s optimal if you can do it all close in proximity, etc. but the ingredients have to be there if it can’t be done on the same day, and that means communication between providers, some way to share in the patient, whether it’s a virtual tumor board or a real tumor board. Those conversations have to take place in order to maximize the outcome for the patient.

MDC CRPC:  Key Ingredients

Again, the ingredients are listed here. I know that many of you who do these know the importance of the navigation, nurse practitioners, and physician assistants cannot be overestimated in this situation. Meetings, depending on availability how often, but more is better than few. If possible, a shared EMR. One of the biggest barriers we have is collating and accumulating all of the information that comes across the fax machine. Again, it lends itself to larger centers or shared EMR if possible. Primary care, now medical oncology may be comfortable managing some of the hypertension and some of the other things that come up, but having a primary care engaged and knowing that they’re receiving the information that you’re doing is also very helpful along with supportive services, and that can be nutritionists, it can be pain management. Certainly palliative care when it is required. So, all of that stuff has to be known, available to you, and you have to be anticipating how you’re going to get them to those next steps.

Lesson #3

The next step is, if you’ve developed this system for managing them, how are you going to deliver the treatments and the therapeutics and organizing your thoughts around the sequencing.

National Comprehensive Cancer Network

There are lots of guidelines out there. They really speak the same language. So, you just have to figure out which one is user friendly for you, and that’s what we tried to do with the AUA guidelines is make them algorithmic or simple because there isn’t really guidance on where it’s appropriate, which one should go first, so that is going to be left to interpretation of the treating physician. But the reality is these things are evidence based. Some have a little bit more to them than others.

American Urological Association (AUA) Guidelines

I’m partial to the AUA guidelines because I think that they were truly evidence based, but they are in constant need of revising, and this year will be no example.

mCRPC Changing Landscape

Dr. Crawford showed this a little bit earlier, and this is that roller coaster slide, which patients don’t like because it is an uphill battle for them as they progress through these various treatments, but when you have all of these different treatments available to you, you have to think in your mind, okay, where is the patient in the journey. Are they hormone naïve, or have they ever seen these types of treatments, are they castrate or endocrine resistant. Do they have metastatic disease or not, and then what are the treatment options available to them?

mCRPC Success Since 1996 Leading to FDA Approvals

There are many treatment options available, the skeletal related, bone health agents were mentioned earlier. Of course those reduce risks of skeletal-related events and can improve on things but they have not extended life. We have certain treatments that are available for pain management including some of the radio nucleotide therapies that were talked about before, except radium, which does extend the life, and then you have survival improving treatments, which are chemotherapies, androgen access as well as the nucleotide therapy of ramucirumab. So all of those are important.

Treatment Evolution

They are all options on the menu. In 2004, docetaxel got approved and things started to happen. There was a drought. About seven years later a second-line chemotherapy and then we started filling in the blanks with some oral agents that were approved post chemotherapy followed by agents that were—the same agents tried in a pre-chemotherapy setting. Radium came along, sip T came along, but we have been a little bit in a drought for a couple of years while we wait for the next step. And while Lenny Gomella said it’s the year of the Eagles, we’ll wait and see about that. I think it is the year of the M0, because now we’re going to start seeing some activity in a space where we’ve had no treatments before. So I’m excited about that.

Index Patients

We, when we made these guidelines, developed them based on partly on the ways the FDA approved these agents, and partly based on the clinical recognition that the presence of absence of metastatic disease was important. The degree and severity of their symptoms was important. Performance status was critical. We can’t give these drugs to everybody, and again, in the beginning when drugs were being approved prior docetaxel was sort of mandated to get the ball rolling, and that has changed a lot over the years.

Index Patients

So there were six index patients and those are there for you to read.

Index Patient 1

This M0 patient which was the ARS question is the unmet need, and 75% of you already knew that we have nothing really approved in this space yet. So things get done for these patients but they are really just kind of manipulating the PSA a little bit and not really extending their life or really changing anything. So we’re excited about this, and this will be updated as soon as the data comes forward, we think, in a couple of weeks we’ll get the presentations, the publications should come pretty quickly thereafter, and then we’ll be in business.

Index Patient 2

For the most common patient who has early metastatic CRPC, those with asymptomatic or minimal symptoms we have a lot of options. So there’s abiraterone with prednisone, enzalutamide, docetaxel. We can give sip T so all of those are options for those patients, and if you’ve been doing some of the things that we’ve talked about like Dr. Crawford was mentioning, really monitoring those patients to see where they are at, you’ll catch them before symptoms are plaguing them and they lose their eligibility for some of these treatments.

Abiraterone:  COU-302

I’ll just briefly say that the COU-302 trial was the second trial for abiraterone plus prednisone, and it did demonstrate not only a survival advantage as well as progression-free survival advantage in patients with metastatic castrate resistant disease prior to chemotherapy.

Abiraterone:  COU-302

Enzalutamide:  PREVAIL

The enzalutamide PREVAIL trial, similarly, was the second big study for them, and it was compared enzalutamide to placebo, again showing significant survival advantage and radiographic progression-free survival in men prior to use of docetaxel.

Enzalutamide:  PREVAIL #2

So these were game changers really because before these two trials came out, we waited until they progressed through docetaxel to even begin to give them their treatment.

Docetaxel:  TAX-327

Docetaxel was the original chemotherapy that showed benefit in survival. It was a three-week, every three week regimen, and it was compared to weekly and it was compared to mitoxantrone, and I think sometimes we forget that. It wasn’t compared to placebo. It wasn’t compared to water because when you look at the overall survival you see there is benefit and it translated only into an average somewhere around 3 to 4 months.

TAX-327 Overall Survival

But what would have happened if they had received no chemotherapy, and what would have happened if they received the chemotherapy earlier? Those are questions we’re starting to understand now that docetaxel is being used in an earlier stage in the hormone sensitive area.

Sipuleucel-T:  IMPACT

The use of immune-based therapy, the only immune-based therapy approved for prostate cancer, SIP-T with its IMPACT trial was a significant improvement. They were a little narrow in their approval, so it is really reserved for those minimally symptomatic and asymptomatic patients, and so in that group there was a significant survival benefit.

Sipuleucel-T:  IMPACT #2

And so that is where it’s used, but once they determine that they are having symptoms, especially enough for narcotics, it’s really hard. We’re fighting an insurance battle as I speak, because a patient was taking some narcotics for his knee. Had nothing to do with his cancer, but they saw it, and they don’t want him to get approved for the SIP-T we’ve already administered. So, we’re having to go back and explain to them this narcotic wasn’t for his cancer, but it’s an uphill battle when you have that happen.

Index Patient 3

Index patient 3 were those patients with symptoms, usually in the studies it was described as pain, but there were many symptoms of metastatic disease. And in there, the same options exist with the exception of SIP-T, which drops off when they’re symptomatic.

Index Patient 3 #2

Additionally, Radium 223 is an option for these patients who have bone lesions, no visceral metastases and it’s approved both in the pre-chemotherapy as well as in the post chemotherapy space.

Radium 223

Lenny showed this study earlier, so I don’t have to really go over it except to say that it was best standard of care compared to radium, best standard of care.

Radium 223 #2

Survival benefit first time seen using radionuclide. All of the other stuff we had before was toxic and palliative, and so this was an advance forward.

Index Patient 5

Index patients 5 are the patients who have seen prior docetaxel chemotherapy. Many of the patients that we’re going to see going forward will have seen docetaxel before.

Cabazitaxel

Cabazitaxel is a salvage regimen. Some people are using it up front, and maybe Dr. Petrylak will talk about that, but it got approval as a second-line therapy in that setting.

Cabazitaxel

With again significant survival advantage compared to mitoxantrone post docetaxel so it is an option.

Post Chemotherapy Clinical Trials

And then as I mentioned earlier, abiraterone, enzalutamide, as well as radium plus cabazitaxel, are all options for men who have been through and progressed through the docetaxel.

Future Directions:  M0 CRPC

Future directions, really the M0 space, and that is where we’re headed. So, I hope next year, when we’re at this meeting we’ll have lots of good stuff to show you, but right now these are the trials.

M0 CRPC – PROSPER:  Enzalutamide

So most of us are aware that enzalutamide has a trial looking at the M0 space called PROSPER, and it randomized those men with no radiographic evidence, and the outcome that they’re looking for here is metastatic free survival, so that is an important thing, different than overall survival, which was the approval for most of the other drugs that we looked at.

M0 CRPC – ARAMIS:  ODM-201

There is another agent, ODM-201, the Aramis trial, which also is in that same space, similarly designed placebo versus the agent gaming for metastatic free survival.

M0 CRPC – SPARTAN:  ARN-509

And then finally there is a third one out there, ARN-509 the SPARTAN trial. So three agents all going after that same patient population, all with that metastatic free survival endpoint along with secondary endpoints but it will be way too soon to see any overall survival.

Spectrum of Disease

So the spectrum of disease is shown here, and unfortunately, for patients, they don’t like it. The treatments are moving back, so we started with end stage, post docetaxel, pre-docetaxel, now we’re moving into the M0. We’ve already moved on the other side of the equator, when patients present with newly metastatic disease. When the guidelines get revised by the AUA, there is a bigger move afoot to do more of an advanced prostate cancer guidelines now that we have good data from STAMPEDE, CHAARTED, LATITUDE, in addition to these new agents in the M0 space. So, I think 2018 will be a banner year again for improving the outcome for patients with metastatic castrate-resistant disease. I think that our goal here is to try and make sure as many as we can of the urology large groups, small groups, academic, private, that they understand these treatments, and we’re really the messengers and the primary caretakers of these patients.

Conclusions

So in conclusion, urologists should be the primary caregivers for these men with advanced prostate cancer, establishing multi-disciplinary clinic is an important component to this, and you have to cobble together the resources that are available to you based on your own situation. We have lots of good therapeutics in an area where we had no therapeutics before and lots of things to offer patients. Do they cure them? No. But will they help them? Yes. And when you’re in that situation, you are going to want somebody to help you, too, and these are important advancements for them. And so the guidelines are going to be updated, NCCN I’m sure, the AUA guidelines for sure, and we hope that they will be more robust than what we were able to do the first couple of times, based on what was out there. So, I finished a little on time, which is not a problem around here, and thank you for your attention.

Question from the Audience:

Mike, that was a great presentation. We use the AUA as well as having the NCCN side by side. I think that navigating through the AUA guidelines is much easier, and the reason that the NCCN classically they were quick to respond to new things that are happening. I’m glad to hear you say that you’re going to get something on the M0. And hopefully, you’ll get in the hormone sensitive space with the CHAARTED and the LATITUDE trials to help all the clinicians out. I don’t know, are you going to try to get that on for 2018 also?

Dr. Cookson’s Answer:

The plan is to go in and have as much as we can – – this year. So, I don’t know the publication dates yet, and just presenting something in abstract form won’t be enough to move the needle, so the publications will come, I think, at least two of them soon. We already have enough of the data to do the advanced prostate cancer stuff, so the goal I think is to have something new by AUA time which is early May. So that is the plan. You are right, because of the mechanism in place for the evidence-based data dredge that they do with a company out of the Mayo Clinic, it has been a little slow to react. I find the NCCN is almost like a compendium. If it becomes FDA approved, it like, fits right in the slot. They know they need to be better about it and more nimble, and I have tried to encourage that.

Leonard G. Gomella, MD, FACS, presented “Bone Metastases and Mortality — Can We Be Doing More?” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado

How to cite: Gomella, Leonard G. “Bone Metastases and Mortality — Can We Be Doing More?” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/Bone-Metastases-and-Mortality/

Summary:

Leonard G. Gomella, MD, FACS, discusses bone health issues related to prostate cancer, specifically androgen deprivation therapy (ADT) induced osteoporosis, bone resorptive therapies, such as bisphosphonates and denosumab, and morbidity and mortality associated with men who manifest bone-positive metastatic prostate cancer.

Bone Metastases and Mortality — Can We Be Doing More? – Transcript

Click on slide to expand

Economic Burden of CaP to Bone

We all know that there is a big problem when prostate cancer spreads to the bone, but we also have a spectrum here. We have to remember that many of these men undergo many years of androgen deprivation therapy and are subjected to the bone mineral density loss and increased fracture risk.

Bone Health Issues in Prostate Cancer

So we’re going to break this into two pieces, the talk into two parts. The first talk we’re going to talk about basically ADT induced osteoporosis, and in the second part of the talk we’re going to talk more about morbidity and mortality associated with men who manifest bone positive metastatic prostate cancer.

Proportion of Patients with Fractures 1 to 5 Years After CaP Diagnosis

So, the number of patients with Fractures 1 to 5 years after prostate cancer diagnosis goes up, but it goes up more as we know in men who are on androgen deprivation therapy, and very significantly the hospitalization risk is also much greater in men on ADT who suffer any type of fracture.

Survival After Hip Fracture

This to me is one of the more interesting graphics. When you look at the survival after a hip fracture, and you look at men versus women, men do much worse after a hip fracture. For whatever reason, it is much more debilitating, and they are more likely to die from their hip fracture than are women who suffer the same fate.

Men on ADT are at Increased Risk of Fracture

Men on ADT we know are at fracture risk, we think as urologists, and this goes back and forth over the years that we tend to underestimate the fracture risk in our patients. Many times they will go out and have a wrist fracture or an elbow fracture and they don’t mention it to us, but clearly all the large data sets show that the men on ADT do have this increased fracture risk, and it is associated with the duration of time on ADT how much bone loss because it is variable, some men lose a lot of bone mineral, a lot of other men lose less and of course the age. The older you are just naturally you are going to have more osteoporosis.

Prevalence of Osteoporosis Increases with ADT Duration

And again, increases with ADT duration, and again, as time goes on and today men are on ADT, thanks to our mCRPC advances, longer and longer and longer, so this is something as time goes on that’s going to be more and more of a problem.

Diagnosing Osteoporosis

Diagnosing osteoporosis, again, everybody knows it is the bone mineral density, it’s the gold standard to determine bone strength, and it is highly correlative with fracture risk, and some people say it is just like a blood pressure for monitoring and following hypertension.

WHO Criteria for Osteoporosis by DXA

These are the WHO criteria on dexa scan. It goes from -1 and above, once you get down to less than -2.5 on the T score you are diagnosed as having osteoporosis.

WHO/FRAX Risk Assessment

This is the famous WHO FRAX Risk Assessment. Anybody can get on this website, you can go in there, and this gives you the ten-year probability of having a fracture and again it depends on how much of a purist you are in running your patients through, deciding who needs the support or who doesn’t. You can go ahead and do this risk assessment.

Osteoporosis and Bone Metastasis Prevention and Treatment

So basically, for both osteoporosis, and we’ll talk about in a couple of minutes, bone metastasis, there’s prevention, and there’s also treatment, so basically, the mainstay, if you do anything at all, the mainstay are common sense things, avoid alcohol, avoid smoking, physical activity, healthy diet, healthy lifestyle, but vitamin D supplementation and the recommended dose right now is somewhere between 1000 and 1250 IU using vitamin D, but again you have to have calcium along with the vitamin D for it to be beneficial.

Osteoporosis and Bone Metastasis Prevention and Treatment

Calcium supplementation has been an interesting moving target. It used to be take as much calcium as you want, but there has been studies out there that showed that men who take too much calcium, greater than 1000 a day, maybe at increased risk of a cardiovascular mortality, and it may be as much as 20%. So, this is a little bit of a caution to us when we sort of over-dispense calcium. So basically, in my world, I think the best OTC choice is the Caltrate, which is 600+ D3, it gives you 800 IU cholecalciferol and then they recommend getting the rest of that calcium from your diet. Of course, bisphosphonates have been a wonderful breakthrough available the last 15 years or so, they inhibit osteoclast activity, reduce bone resorption, and they can increase the bone mineral density. It doesn’t seem like very much, but when you take that 5% increase to 8% increase in the spine and you put it in the facts it really makes a major impact on that patient’s 10-year fracture rate. Of course the dental exam very important before starting and actually it is recommended by most organizations to continue that exam every six months while the person is still on the bisphosphonates.

Common Bisphosphonate Side Effects

We know bisphosphonates, oral agents can cause a lot of side effects. We’ve got to tell patients, “Make sure that, you know, you sit up for at least a half-hour or an hour after you take the bisphosphonates.” There are some older folks who get that stuffed in their esophagus, and get esophageal burns and perforation, but the class warning for all bisphosphonates is bone, joint and muscle pain, osteonecrosis of the jaw, ONJ, which if anybody has ever seen it, is one of the really most horrifying side effects of anything that we do, and this very rare and it was mentioned the other day about atypical fractures of the femoral shaft, which no one is able really to sort out what is going on.

Denosumab

The other thing that we have out there is the RANK ligand inhibitor denosumab that also increases bone density by about the same amount over several years, and it reduces the incidence of vertebral body fractures by about 70% and hip fractures by about 40%.

Common Osteoporosis Agents in Men

A whole variety of osteoporosis agents are out there. Some of them are labeled specifically for men. Some of them are not labeled specifically for men with ADT induced osteoporosis, but again the choices are out there. I think probably the most common one used in the United States is Alendronate 70mg once a week.

Two Forms/Indications of Denosumab

We have two forms of denosumab as everybody is aware of, and this is where you have to actually use the brand names when you discuss these because while they are both denosumab they are completely different indications and completely different volumes, and when it comes to the dose. So Prolia is specifically for men on androgen deprivation therapy and to manage osteoporosis both in men and women and that is the 60mg subcu every six months. However, once you move over to patients with documented bone metastatic disease, the formulation then goes over to Xgeva, and that is basically 120mg subcu but that is given on a monthly basis.

National Osteoporosis Foundation Fracture Prevention Guidelines for Men

National Osteoporosis Foundation really wants us, and this is a general statement about men’s health, look at really the risk of a man having significant morbidity and mortality. Think about medical-based therapy if you have any man in a men’s health clinic regardless of prostate cancer if he has had a vertebral body or hip fracture. If he has a low T score, and again if he has a FRAX probability of a hip fracture, or any other significant fracture, think about putting these patients on some type of medical based therapy. Again, as urology gets more into men’s health and as men are living longer, and longer, these are some areas that we’re going to have to be a little bit more aware.

Healthy Bone Program:  ADT hip fracture reduced >70%

There are programs that have been out there. There are many out there. One was just reported about a week ago using different approaches, but it showed the same thing, that basically these different programs that are out there recommend dexa scans for all men greater than the age of 70. This is regardless of their ADT. If a man is over 50 and he is on ADT, it is recommended that he has a dexa scan, and that is repeated every five years with changes in the approach based on how bad their osteoporosis is or if it is reversing, but again, the common sense thing, smoking cessation, regular exercise, adequate calcium intake, and adequate vitamin D. All common sense things that should be used along with these agents.

Bone Health Issues in Prostate Cancer

In the last couple of minutes, we’re just going to talk about the morbidity and mortality of these—what happens when men develop bone metastatic prostate cancer.

Skeletal-Related Events and Clinical Consequences of Bone Metastases

And we talk about SREs or skeletal-related events, and this is just sort of a partial listing, pathologic fractures, cord compression, the need for radiation therapy or surgery to the bone, are the standard SRE definitions that you will see in the literature. However, other definitions may exist out there, but those are the hard core ones that, when we talk about most of the studies that look at bisphosphonates or denosumab in reducing fractures. talk about that group of limiting those skeletal-related events.

Impact of Prostate Cancer Bone Metastasis on Survival

If a man has bony metastatic disease, you can see clearly a major impact on survival with very grave outcomes historically with bone metastatic prostate cancer.

Site of Prostate Cancer Metastasis and Survival

What is very interesting, if you look at this, is another very interesting curve. If you look at the survival, the mortality increases as you go from nodal disease, to bone, only to visceral, to finally bone plus visceral, which is some of the most lethal combinations of metastatic sites in prostate cancer. But clearly, the bone problem is much worse than the lymph node problem, I think, as most of us are aware clinically.

CaP And Bone Metastasis

Now, this new area, which again is getting a lot of press, and there’s a lot of companies that are involved in CAR T-cell therapy. Over 90% of men with metastatic castrate resistant prostate cancer will have identifiable bone metastasis, and again, we mentioned the skeletal related events associated with metastatic bone positive prostate cancer or cord compression, pathologic fractures, and the need to have either surgery or radiation for one of those fractures. The anti-resorptive and bone-targeted therapies that we talked about denosumab and bisphosphonates, it’s not really clear that they do improve survival, but it is really clear that the skeletal-related events in the majority of studies are positive, and that there is a benefit to limiting the SREs that we talked about.

Cap And Bone Metastasis

So, about 50% of men with castration resistant prostate cancer will develop mets within two years of CRPC diagnosis. This world is going to completely change, as Dr. Reiter talked about yesterday, the new PET imaging agents are going to probably change our approach to a lot of these, but the big number we have is more than 30% of men with purely castrate resistant prostate cancer thought to be M0. If you study them close enough, you will find that that group about a third actually do have metastatic lesions, and that is dependent upon how quickly or how frequently you image these patients.

RADAR Study

And this is Dr. Crawford’s famous RADAR paper, that many of us in the room participated in, that gives you the goal of identifying patients with metastatic castrate-resistant prostate cancer early, so you can offer them some of the advanced therapeutics.

Alk Phos and PSA: Predict risk of Bone Mets

So interestingly, a very simple alk phos, most of us don’t do it, but actually looking at alkaline phosphatase is something. I think those of us that treat advanced prostate cancer need to think a little bit more about because it does have very significant prognostic implications in predicting the risk of bone metastatic disease. So patients with a low PSA of less than 20 and an elevated alk phos it can be used to identify the patients who are going to be at risk for developing and progressing on their bone metastasis.

Bone antiresorptive therapy with MI disease

If we turn to the NCCN Guidelines, they clearly support the minute you have castrate resistant prostate cancer with identifying metastatic lesions in the bone, it is strongly recommended that you or actually they say consider bone resorptive therapies with either bisphosphonates or denosumab in that group of patients.

Phase 3 Study of Zoledronic Acid Versus Denosumab; Time to First SRE

If you look at zoledronic acid and you are thinking, well, should I use zoledronic acid, should I use bisphosphonates, again not a lot of data out there, but there is this one paper from Lancet that showed there was a slight improvement in using denosumab over bisphosphonates in the time to the first skeletal related event.

Zoledronic Acid Versus Denosumab:  Adverse Events

Zoledronic acid versus denosumab, if you look at the adverse events, they are pretty much the same. I think most of us remember I guess it was five or six years ago when denosumab came out, we thought this scary boogey man the ONJ with the bisphosphonates was not going to be present with the denosumab but it does turn out that it is present in both of them, so whether you are using denosumab or one of the bisphosphonates, you’ve got to be vigilant for osteonecrosis of the jaw. However, when it comes to hypocalcemia, denosumab is more likely to cause a patient to become hypocalcemic, so when the men are on these medications, obviously you need to do periodic measurements of calcium levels.

Bottom Line:  Radium-223 is Short Range but Deadly

Dr. Koo gave a very nice talk on Radium 223 and focused mostly on its survival advantage when it comes to the treatment of metastatic castrate-resistant prostate cancer.

ALSYMPCA

And again, Phil showed this yesterday, showing the improvement in overall survival but we’re talking about it today in the context of improving the morbidity and helping patients and if you look at the ALSYMPCA study the first symptomatic SRE was greatly improved through the use of Radium 223. So, not only does it have benefit in the survival category, but it also helps us with some of our skeletal related events.

Radium 223 and Bisphosphonates:  No Combined effect on Survival in ALSYMPCA but positive effect on Symptomatic SRE’s

And, in fact, if you look at Oliver Sartor‘s paper where they took the ALSYMPCA data, and they looked at patients on Radium 223 and bisphosphonate, no real impact on survival, however, you can see that there was a highly statistically significant improvement in skeletal related events, so if you have a patient who is on bisphosphonates and they go on Radium 223, you should probably consider continuing those drugs.

Radium 223 Label

The Radium 223 label is indicated for the treatment of patients with castrate resistant prostate cancer who have symptomatic bone metastasis and no known visceral or metastatic disease, so they don’t specifically talk about reducing skeletal related events, but clearly, most of these patients who are on Radium 223 are on the drug to help improve their overall outcome and survival.

How I Do It

You’re getting the extra hit, the extra benefit of perhaps limiting some skeletal related events in these men. The recent abiraterone Radium 223 debacle notwithstanding in that regard. If you’re not using Radium 223 we have a nice paper that came out a couple of years ago that gave you the nuts and bolts of how to start using Radium 223 in your practice.

Conclusions

So the bottom line in patients on ADT, again consider monitoring dexa. We realize that the insurance company’s a real pain in the butt when it comes to getting it approved, but if you’re going to be serious about it, you should probably monitor Dexa scans. We have a hard time in Pennsylvania, unless somebody has proven osteoporosis on a Dexa scan, they won’t approve a Dexa scan, Blue Cross and Blue Shield, so tell me how that works. I don’t know. It makes it very difficult for us. Strongly consider some type of antiresorptive therapy in men with mCRPC. Radium 223 is useful in patients with symptoms and can have significant protective effect, and again you need—if you are going to use Radium 223, you need to have significant institutional support, and the infrastructure to make sure that you can administer it properly.

Scott B. Sellinger, MD, FACS, presented “A Value-Based Health Care Model and PCa” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado

How to cite: Sellinger, Scott B. “A Value-Based Health Care Model and PCa” January 27, 2018. Accessed [date accessed]. https://grandroundsinurology.com/A-Value-Based-Health-Care-Model-and-PCa/

Summary:

Scott B. Sellinger, MD, FACS, explains how the constantly evolving Medicare Access and CHIP Reauthorization Act (MACRA) affects Medicare payments to urologists, and how urologists can participate in the Merit-based Incentive Payment System (MIPS). He also discusses the Large Urology Group Practice Association’s (LUGPA’s) efforts to develop urology-specific advanced alternative payment models (AMPs).

A Value-Based Health Care Model and PCa – Transcript

Click on slide to expand

Payment Reform in US Healthcare

So payment reform in US Healthcare. It came about by need for cost containment. Everybody knows that. It’s driven by CMS and Medicare. This whole idea of switching from volume to value-based care, and that really was the birth of MACRA, and we’ll talk more about each of these.

Value is Defined As:

Value is defined as quality over cost, so the higher the quality the higher the value. The lower the cost, the higher the value as well. And the whole goal here is to have high quality, low cost health care, and that would equal best value.

The Sustainable Growth Rate (SGR)

The sustainable growth rate, which most of you should be familiar with, we heard about it for about 20 years, and that was a concept that was significantly flawed, the overall physician costs if they were greater than the target Medicare expenditures, then physician payments got cut across the board, and every year we were faced with significant up to 20, 22% payment cuts if there wasn’t this so called “doc fix.” Of course it really wasn’t a doc fix, there was nothing wrong with the doctors. It was a government fix that really was the problem, but no fix in 2015 would have meant a 21% cut in Medicare payments to clinicians, and of course it did get fixed at the last second, as it always did.

What is MACRA?

So where did MACRA come from? MACRA is known as the Medicare Access and CHIP Reauthorization Act of 2015, and it repealed this whole sustainable growth rate formula. MACRA is here to stay. It’s not going anywhere. We’re going to talk about the components of it that may be in jeopardy, but the concept of MACRA was 90% bipartisan support in Congress. It was supported by Republicans, by Democrats, it was supported in the House and in the Senate, overwhelming support, and this is not going to go anywhere. The SGR was replaced by the quality payment program, which is within MACRA, and you have your two tracks. You have your MIPS track, which is the merit-based incentive payment system, and them the other track, which is the advanced alternative payment model, so I’m going to talk mostly about MIPS today because you’re going to hear more from Dr. Henderson tomorrow about the APMS.

Participating in…Is similar to…

So where did these come from? You’re familiar with PQRS. You’re familiar with the value modifier and the EHR, which was meaningful use. That was what we are participating in currently up until our payments are changed in 2019. In the new system, in the new MIPS, PQRS is very similar to quality. The value modifier is really our cost component, and EHR is not called Advancing Care Information.

Quality Payment Program Tracks:  MIPS and Advanced APMs

So the payment system starts reporting in 2017, and the payments will begin in 2019, and if you’re in the MIPS arm you will follow this plan. If you are in the alternative payment model, advanced APM arm, you will follow down here, and the bottom line is that starting in 2019, you will be paid based on your reporting in 2017, and you will be eligible for either a 4% increase or decrease depending on how you perform, and then each year along the way that goes up a little bit, up to approximately a 9% bump in the future. If you’re in the APM arm, it’s a 5% incentive payment that begins in January 2019. As I will show you in a little bit, it is going to be—it is difficult for urologists at this point in time to participate in advanced APMs, because the criteria are so strict.

In 2017 You Can “Pick Your Pace” When Deciding on Your Participation Level

So in 2017, you can pick your pace, and your groups have done this I’m sure, but you have actually up until March 31st of this year to report for 2017. But if you don’t participate at all then you just take a 4% cut, you say the heck with it, we’re not going to mess with it at all, and we’ll just take a 4% cut on our Medicare patients, and be done with it. But it’s simple enough actually. You can do what we call test reporting, and with that, you just pick one measure on one Medicare patient, and you actually just need three points, and you satisfy the criteria for minimal reporting, and then you are not in any jeopardy for any adjustment one way or the other. Many practices are doing the partial participation, in that you will be eligible for a modest bump, and then the full participation as well, a little bit higher bump perhaps, although it is still a little bit mysterious what the payments really will be.

Who Can Participate in the Quality Payment Program

Who can participate? If you are an eligible provider, and here they are listed down here, and it turns out 93% of urologist are eligible to participate in 2017, you have to bill more than $30,000 to Medicare and provide care to more than 100 Medicare patients. I would suspect that almost everyone in the room here does qualify.

Eligible Professionals (EPs) Will Begin to Report 3 Out of 4 MIPS Categories in 2017

This is what the components are of MIPS. you’ve got the quality component, the cost component, the clinical practice, improvement activities, and advancing care information. And you are familiar with all of these, because you are doing this now under the previous plans except the new one, which was my ARS question, the clinical practice improvement activities is now added into the mix. We’ll talk a little bit about these here.

The Weighted Value of MIPS Performance Categories Changes Each Year Between 2017 and 2019

There’s weighted value for your score in 2017, 60% is quality, and you’ll notice here the big difference is that there is no cost component in 2017. It’s being phased-in in 2018 and 2019, and this will be claims-based data so it’s a little bit dangerous where this information will be coming from, but you will be seeing the cost part of this brought into the equation, phasing down the quality component down from 60 to 50, and then down to 30%.

Calculating Your Final MIPS Score for 2017 (Example)

This is how the score is actually calculated, and this is just a sample score. You will probably need your mini computers there to look at this from the back, but the quality is the 60%, cost is 0 this year, you’ll see her because it’s 2017, 0, and then clinical practice improvement is 15%, and you are advancing care, which is your old meaningful use is 25%. The nice thing about these two at the end here is it is really just an attestation, and your administrators will do this for you in most cases. But, you basically just have to say whether you are doing it or not, and you can get full credit for it. Most of the variability is going to be at least in the first year or two in the quality component, and this is what is going to separate out the groups.

Then if you are a high performer, if your score is over 70, which really is not that hard to do if you have good reporting systems, then you will be eligible for the so-called half a billion, 500 million dollars in bonus money that is going to be distributed to all of these high-performing individuals and groups. Now, what percentage of that $500 million you will get remains to be seen. I think estimates now is that it may be up to $1000 or $2000 per person, and maybe even that might be a little bit high, so it is not going to be like you’re going to get a check for $100,000, but it is still to your benefit to be in the high-performing group.

MIPS: Quality Performance Category Requirements in 2017

So MIPS quality it’s 60% of the score, and there is a ton of measures, and I’m not going to go into those today, but your administrators know what they are and will help you with this. You have to select 6, and you may also select specialty specific set of measures, and there are urology-specific measures that you can choose. Here are some of them here.

QPP Quality Measure Set: Urology

Just to give you an example of some of the things that are measured, these are all process measures here. Some of them are what we call high priority, and then there’s cross-cutting type measure which is tobacco use. A lot of groups are using that because it’s pretty easy to measure. Other things that are easy to measure are medication reconciliations, and avoidance of high-risk drugs in the elderly, and so on.  And you just have to pick which measures you’re going to submit and go with them.

MIPS: Cost Performance Category Requirements in 2017

As we stated for cost there is no reporting in 2017. Clinicians are assessed on the Medicare claims data, and this could be, I think, a very dangerous aspect, because it is really totally out of your hands as to who decides what your costs are, and then you will get some feedback, and you’ll see how you do. And it uses measures that were previously used in the value-based modifier and then the resource use report, which was your cost report.

MIPS: Improvement Activities Performance Category Requirements in 2017

So MIPS improvement activities this is the new one, this is 15% of your final score. There’s about 90 activities, and these are the different categories here, and you can see them, just an example of where you can get credit in the practice improvement if you open the practice to Medicaid patients, that is a few points to do that.

MIPS: Advancing Care Information Performance Category Requirements in 2017

Then, the advancing care information, which is the old meaningful use. This is just the exchange of information back and forth, and you just need to attest as a group that you are doing everything that you say you do, and you can get full credit for that.

MIPS Under Siege….Already

Now, having said all that, now we have to see what is going on current day. The problem with all of this is it is really a moving target. Every day the questions are the same, but the answers are different. I think that I could give this talk a week from now, and it may be a different set of slides. It is really unfortunate it’s that way, but that is what we’re dealing with. So MIPS is under under siege. Now, I’m not saying MACRA. I’m saying MIPS. MIPS is one arm of MACRA. MedPAC, which is Medicare Payment Advisory Commission, met in October. They’re 18 members, and I want you to know it’s 4 physicians out of those 18, and the others are PhDs or others of the like. The staff presented options to eliminate MIPS and a new system, where there would be a 2% withhold to all groups, and this would eliminate all of the quality, advancing care, clinical practice improvement measures, and clinicians would be evaluated now based on population-based measures, cost measures, and again claims data, which is not in our best interest to have claims data used as the primary source.

MedPAC Update 12/7/17

They met again December 7th, and Chairman’s draft recommendation said we should eliminate MIPS and go to this so-called voluntary value program, with this 2% withhold, oh by the way this will free up that $500 million per year that we were going to use for those MIPS exceptional performance group, and by the way it’s not likely to affect beneficiaries’ access to care, which of course is the main thing that our leaders are concerned about. Because that’s what leads to an election or non re-election, and significantly reduced clinician burden, eliminates extremes in payment adjustments.

MedPAC Update 1/11/18

And I just put this slide in this week, because they met for the third time on January 11th, and they had their vote, and they voted 14:2 to repeal and replace MIPS. So all of this work that we’ve done, now they say, well, we were just kidding, we don’t really want to do MIPS. Now, this is MedPAC. This is not CMS. This is not Congress. This is an Advisory Commission, and their—their weight in the deal can be questioned. I wouldn’t close up the shop yet. I think it is a recommendation, and it will be taken as a recommendation.

Commissioner Coombs conveyed concerns that the Voluntary Value Program—that none of the professional medical associations actually supported it, but that didn’t seem to matter to the Commission. They said, well we’re still going to go ahead and scrap it. So how much power does MedPAC have? I don’t know, but don’t abandon MIPS yet. Go ahead and still do your reporting. I think it’s in your best interest.

Advanced Alternative Payment Models

Briefly on Advanced APMs, because you’re going to hear more about this tomorrow, but this is the other arm, and it is a 5% lump sum. This is really where they wanted everybody to eventually land in MACRA. MIPS is sort of a stepping stone to get to the APMs, because that is really the true value-based care. MIPS really is not truly value-based. It’s still fee for service with a little bit of quality and other things thrown in. But, you’re still being paid per patient encounter, whereas in APMs it is really moving more towards a value system.

Per CMS, the Following Programs Quality as AAPM in 2017

This is a diagram that just shows who can qualify for advanced APMs, and the oncology care model is probably the one that many of you are most familiar with, and you can see what some of these others are here. But the real problem here with the Advanced APMs is you have to have 20% of your Medicare patients, or 25% of your payments, and that is just very, very hard at this point to have that kind of volume, and those percentages actually increase every two years, so your eligibility to be in the APMs get harder and harder as the years go on. So only 100 urologists in the entire US actually qualified in 2017 to be an advanced APM, and those were primarily associated with the oncology care models.

Oncology Care Model (OCM)

So the oncology care model is an episode of care model. You get payments over a six-month episode. You get a certain amount of money per member per month, and it has two-sided risks, and that is the definition of advanced APM. It’s a two-sided risk model, and ideally, it is intended to improve quality of life and reduce cost, and this is a care coordination and really the new paradigm in healthcare.

The First Urology-Specific APM Proposal submitted to CMS

Now, LUGPA has been really instrumental in moving forward. We feel we want to be on the cutting edge, and we want to beat the government to the punch, rather than them tell us what we need to measure, and the types of models and pathways to develop. We’re going to step up and come to them and say this is what we feel are the best options and we have good data to support it. So the very first IPM proposal was the prostate biopsy, the positive biopsy for localized prostate cancer shifting between active surveillance and active treatment. Unfortunately, this one came back to the drawing board, and will be resubmitted with some additional data.

Joint LUGPA—Integra Connect APM Development Initiative

That is this first one here, URO 1, but the good news is there are about 44 LUGPA practices nationwide that are—that’s about 30% of all of the LUGPA practices that are participating in another APM development, same concept, where we’re using genomic markers for clinical utility purposes to see how it changes what we do and how we manage patients with localized prostate cancer. So, why is this important? Because it’s going to change how you get paid. It’s going to be more of a bundled payment concept for that episode of care that diagnosis, and you’re going to have to choose what you’re going to do with that money, and if you choose very expensive pathway or if you—as one of my colleagues, Dr. Kirsh will say, if you decide to swim out of the lanes, and you don’t follow pathways and procedures, then you are going to be part of that two-sided risk and be on the down side of that two-sided risk. There are other models that are coming up in advanced prostate cancer, biochemical failure in primary care, CRPC, so be on the lookout, and this is something again that LUGPA is working on the cutting edge on everyone’s behalf to try to do the right thing.

MACRA in 2018:  Quality Payment Program for Year 2

So MACRA in 2018 I just want to spend minute on this because we have our next—we already got through the first year, and this is what is going to happen within the final rule that came out for 2018. This will be how you are paid in 2020. Quality will drop, as I said, to 50%, cost goes up to 10%, and the performance threshold goes to 15% instead of three points, so you have to do a little bit more reporting to have the break event point, the 2015 EHRs will be allowed, and I don’t really want to talk much about that. You’ll get some bonus points for treating complex patients. There will be no penalties if you are in a hurricane or disaster area, which was nice of them. Small practices receive 5 bonus points and that’s defined as 15 or fewer.

MACRA in 2018:  Quality Payment Program for Year 2

This is the big one right here though. The eligible clinicians that are excluded and I showed you the exclusion before. It was 30,000 in charges and 100 beneficiaries, well now it’s gone up to 90,000 and 200 so this actually concludes this is not urologist but just the eligible providers. Now, the total excluded providers in the United States is close to a million so that’s 40% of eligible physicians. So you’ve gone from college now to medical school in a sense. It’s getting more difficult. Tech people that you will be judged against of course this is not—you’re not judging against urologist, your judged against all eligible providers so the competition is going to stiffen, and then in addition virtual groups, some additional improvements and then the payment adjustment goes to 5% as opposed to 4%.

BIG News: Part B Drug Payments in 2018

ALICE RUCKART:  One of the biggest parts of this is the Part B drug program. This is really important because the bottom line is this can affect Medicare beneficiaries losing access to care, and that’s the one that thing that Washington will listen to. When we go there, the problem is that if you are on the lower end of a score and you take a payment hit and your Part B drugs are included in that, it is a very significant disincentive for you to take care of those high, those highly complex cancer patients and access to care will suffer because of that. And LUGPA is working very hard with many other associations to eliminate this addition of Part B drugs and not apply it to the payments.

New Urology Quality Measure

Then I’m going to give one shot out to my good friend, Dr. Melhaff because his Oregon Urology Group and he is here today. He’ll be speaking tomorrow and we’ll have some panel discussion, and this was a bone density evaluation for patients with prostate cancer receiving EDT, and it was approved so this was something that our own urology people actually came up with to be used as an electronic quality measure, and we’re really proud that got approved this year, so look at for that in the future.

Philip J. Koo, MD, presented “Update on Radiopharmaceuticals— Choosing a Companion Drug to Radium-223” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado

How to cite: Koo, Philip J. “Update on Radiopharmaceuticals— Choosing a Companion Drug to Radium-223” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/Choosing-a-Companion-Drug-to-Radium-223/

Summary:

Philip J. Koo, MD, describes the mechanism of action of radium-223 in prostate cancer treatment, options for combining and layering radium-223 with other drugs, and how the field of radiation is evolving. He also addresses the controversial ERA 223 trial results.

Update on Radiopharmaceuticals— Choosing a Companion Drug to Radium-223 – Transcript

Click on slide to expand

Disclosures

All right. So my disclosures.

Radium 223 is best used in combination with:

And then, additional disclosure is- I’m a simple-minded nuclear radiologist, but I’m not going to be speaking about imaging. And Dr. Reiter’s talk was awesome, so I don’t think there’s any need to talk about imaging.

Good to Great

Oh, so when I was first invited to give this talk, and I was given this topic, you know, in my mind I was thinking about Radium-223 and I was thinking about all of the experience I had giving Radium-223, and then using the available data to sort of come up with a story that made sense. That being said, things changed on November 30th, when there was an announcement, and we’ll go into those details later. But it sort of reminded me of this book, Good to Great, written in 2001. It was published in 2001.

Good to Great to Good (Gone)

And then, if you look at the various companies that were actually talked about in the book, it is interesting to see how they performed, so it’s good to great to good, or maybe even gone. Circuit City, wow, if you invested in that company based on that book you’d be broke. Fannie Mae was D-listed from the NYCE. Wells Fargo had their own set of issues with fraud, and these companies during the economic recession, actually underperformed the S&P 500 during that time. So, it was kind of an eye-opening lesson that you have to change.

How the Mighty Fall

And Jim Collins being the thought leader that he is wrote a book How the Mighty Fall and I think it’s kind of ingenious that he would follow up with that.

Change

I think we all know that change is going to happen. Change is real, and I think one of the great things about this meeting is that we really embrace change and a lot of discussion about change occurs. I was talking to Jim – – at dinner last night, and he actually made this comment. Coming to this meeting helps him stay three years ahead in his practice, which I think is pretty remarkable. LUGPA now a partner in this meeting clearly is a change meeting, and they’ve talked about various things. They’ve made a huge difference, and now with the APMs I think that urology is in really good hands. Something magical won’t happen if we don’t do anything. We actually do need to act.

The Law of Disruption

When we think about change, I think clearly technology changes much faster than anything else, and then I think social change occurs, next business change, and political change. When we think about change in medicine, I think it actually lags much lower than anything else, which is a concern.

Target on our Backs

Which is a concern, because I think we have a target on our backs. And disruption is real, and if I think about radiology, my field, when I went into radiology everyone told me, oh, why are you going into radiology. Teleradiology, all of your cases are going to be outsourced, and that might have been true, but I think our society embraced the technology and really made it work to our advantage, and artificial intelligence, machine learning, that is real, but we’re taking very active steps to embrace it and use it in ways to actually improve patient care and reduce cost, and I think if we all—urology the same thing, advanced prostate cancer clinics, and the changes that are undergoing in urology have really helped us and create a roadmap for the ways that we can change from our societies perspective.

Targeted Alpha Therapy

That being said, we’re going to talk about targeted alpha therapies and Radium-223, and this sort of lists out some of the other drugs in that CRPC space.

Back to the Future

This is really going back to the future, because these systemic unsealed sources of radiation that we’re injecting were actually used in the past, but we’re re-visiting them, and I think there is a lot of potential for these in the future.

Radium-223

You inject it intravenously slow over one minute. It circulates throughout the body, and then it is going to localize to bone. It’s going to localize to areas that have metastatic disease to a higher degree because there’s greater perfusion to those areas, and the surface area of bone in those areas area actually going to be greater. Once it localizes to those lesions in bone, it’s actually going to give off this alpha particle, and create these double-stranded DNA breaks, and there’s actually small animal models that talk about Radium-223 causing changes in the tumor microenvironment that make it less hospitable to mets for the future.

Alpha Range – Beta Range

This is sort of the real key to how these alpha particles work. The alpha particle, you notice that the particle mass is multiple, multiple times greater than beta emitters, which is what we use in a lot of other therapy. So it is like getting hit by Mike Tyson as opposed to Floyd Mayweather, which by the way Floyd Mayweather he is a great boxer, but clearly he doesn’t have a lot of power. It’s range in tissue is much shorter, so that is significant because the radium is going to stay localized to the areas that it lands as opposed to beta particles which are going to go much further and affect healthy marrow cells, which is something that you don’t want to do.

Improved OS

That is why we saw this improvement in overall survival from the ALSYMPCA Trial that—but we also saw an increase in time to your symptomatic first symptomatic skeletal event, so there was sort of this bone protective aspect to Radium-223 as well.

The Technology Adoption Curve

So I think it was approved four or five years ago, and we’re seeing more and more adoption of this.

How do we adopt change?

We’re seeing greater acceptance and greater ownership of this, and it was interesting to hear Dr. Crawford at the first talk, where he talked that there were actually 54 clinical trials actively using Radium-223 on clinicaltrials.gov, so I think that is a sign that we are really trying to dig deeper into how we use this.

The Search Begins…

All right. So let’s start the search. Why are we starting the search?

Why?

I think the search for a combination therapy or a therapy that you use together really makes sense for Radium-223 because of the mechanism of action. It localizes the bone, and it is really disease agnostic. It just gives off an alpha particle wherever it can, and causes DNA breaks if there are cells there. So it is bone targeted. A problem with Radium-223 is that PSA rise, right, so you do see a slow rise in PSA, and we know that is probably coming maybe from other cells like other tissues, like soft tissues, nodal disease, and what not, so it makes sense to find something with a different mechanism of action where you can target various sites of disease. I think the other reason why it makes sense is because the drug has been proven to be safe in the ALSYMPCA trial.

Effect

So, when we look for some sort of combination therapy, I think ideally you find something that is synergistic. And this comes from a multiple sclerosis website. If it’s additive, that’s not bad either. In this case, if you have something that is hitting the bone and something that is hitting the soft tissues, and they are additive, that works as well. Clearly, you don’t want something that is antagonistic, in which case, you wouldn’t move forward with such a therapy.

Radium-223 Plus Targeted Therapy

So we’ll start off with Radium-223 plus Targeted Therapy, and this morning, hearing Dr. Glode’s talk on PARP inhibitors was great for me, because it really opened up my understanding of PARP inhibitors.

PARP Inhibitor Plus Radium 233

And there are currently a couple of Phase 1B and Phase 1 and 2 trials looking at PARP inhibitors, and this makes sense. You know, if you have Radium-223, these alpha particles that can cause double-stranded DNA breaks, there are going to be times when it only causes single-stranded DNA breaks, and in those cases, if you have the combination with a PARP, it makes sense that you will lead to more cell death.

NMC

So, we will await the results from that. So, that led me to think, all right, imaging. I think a lot of times, we don’t really use imaging to assess response, especially in prostate cancer, but this is something that we did for targeted therapies, BRAF, MEK inhibitors in melanoma where we actually had baseline scans, follow-up scans, and we actually looked at response and correlated that with overall survival. So, I think the further we go along with these targeted therapies and combination therapies in prostate cancer, I would encourage some of the scientific people in this audience to think about ways that we could incorporate some of these newer imaging technologies into our protocols.

Radium 223 plus Immunotherapy

So radium 223 plus immunotherapy. Dr. Concepcion gave a great talk in immunotherapies, and I’ll be honest.

The Abscopal Effect

This whole experience has been very humbling. Medicine has been very humbling, and I remember when I first heard about the abscopal effect, I laughed. I thought that is impossible. That makes no sense at all, and I just sort of really dismissed it. Shame on me. We started seeing cases like this, and this case comes from the literature, where you had a liver lesion that was treated with external beam radiation, and that liver lesion was gone on a follow-up PET CT. Interestingly, a lesion in the left lower lobe of the lung disappeared even though it wasn’t radiated, and this lesion in the left sacrum also disappeared, and that is sort of the idea of the Abscopal effect. It’s a little different, because the abscopal effect was really meant for targeted therapy to a single lesion that releases antigens, and Radium 223 is a little different, because it’s systemic.

CCR Translation

The whole idea is you know, you have radiation, it releases various inflammatory mediator cytokines, antigens, and then if you can combine that with something that stimulates the immune response, it could lead to greater targeting and attacking of the cancer cells.

Sip-T Plus Radium 223

So, there are several studies looking at this currently. There is a Phase 2 trial that was originally scheduled to complete in December of 2018. I think it might be a little delayed from what I hear, but it is going to look at peripheral T-cell proliferation, immune response, safety, PSA, alk phos, radiographic and clinical progression, and time to chemotherapy. So, I think this holds a lot of promise to see, when done together, if there is actually an improvement and a synergistic effect to the two, which would be very promising.

Pembro/Atezo

So, then you have the PD1 and PDL1 inhibitors that are actually being used right now in clinical trials, but those won’t be completed for a little later, but it’s encouraging to see the use of some of these other, more second generation immunotherapies used in clinical trials with Radium 223.

March-April 2015

The discussion of radium 223 really brings into—it gives us the opportunity to talk about immunotherapy and radiology, and I think this is something that we’ve noticed and gave us an opportunity for a former colleague of mine, Jennifer Kwak, to write a great review article about this in RadioGraphics, because you will see immune mediated adverse events. And oftentimes, they will show up on the scans that you get for follow-up, CT scans. You will get colitis, which can be life-threatening, you will get hypophysitis, you can get various things, pancreatitis, just inflammation to normal cells, and it’s important to recognize that these aren’t signs of disease progression. It’s just actually the drug working, and in fact there was a study published in the American Journal of Radiology that talked that the greater number of immune adverse events you had on imaging, the better the response was clinically. So, I think it is something to be aware of. Oftentimes, things will look stable before they get better, or things could potentially look worse before they get better. Be careful if you see something that talks about progression, especially if it is a single time point. One thing we always request—well, we don’t request it since we’re on the same EMR, but we often—we look through the medical record, we look when they started immunotherapy, because that will have a huge impact as to how we interpret those images. So for those of you practicing, make sure that you have a good working relationship with your radiology team so they understand that.

Radium 223 Plus Chemotherapy

All right, so Radium 223 plus chemotherapy. This was one area that I really sort of was incredulous, and I didn’t think this would be successful.

Docetaxel Plus Radium 223

So far, the preliminary data shows that it could be safe, and maybe it has some efficacy. So, Phase 1/2a trial had five doses of Radium at 50 kBq, I think right now it’s 55 kBq’s every six weeks in combination with a reduced dose of docetaxel. This was administered intravenously every three weeks.

Prostate Cancer—Advanced Disease

This was from, I forget, GU ASCO maybe a year or two ago, I think two or three years ago, talked about the safety profile, that it was actually safe, and they saw a response in the total alk phos, and P1NP, which is a bone turnover marker, so again I think this actually holds some promise.

Phase III

Again, I think this actually holds some promise, and Phase III trials I think are currently in development looking at metastatic castration sensitive prostate cancer, and those patients will get hormones, docetaxel and radium versus hormones and docetaxel. And also in CRPC, we’re looking at docetaxel vs docetaxel plus the radium.

Radium 223 Plus AR Inhibitors

So Radium 223 plus the AR inhibitors, this was sort of the low-hanging fruit, and I think most people would agree, when we were thinking about this year ago, this was sort of the easiest hurdle to overcome, and this was probably the first combination that would be approved.

Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer:  an international, early access, open-label, single-arm phase 3b trial

This comes from the expanded access trial. Fred Saad published this et al in Lancet Oncology in 2016. This I think included maybe 7 or 800 patients that actually showed that it was safe in patients who actually received abiraterone, enzalutamide, and denosumab with Radium 223. Not only did they find that it was safe, they actually saw some findings that suggested a prolonged survival in those patients that actually received abi, enza, and denosumab, with the Radium 223. This was designed similar to ALSYMPCA where patients were given Radium and kept on their normal standard of care therapy. In ALSYMPCA I don’t believe any patients received abi or enza.

eRADicAte

So there’s eRADicAte, and this comes from Dr. Shore, open-label, Phase II trial. I think it might have been 30, 40 patients, patients were given radium plus abi and prednisone. This was CRP patients with symptomatic bone mets, and they looked at bone pain and quality of life.

BPI-SF

They also reported that it was save. The pain severity score decreased in 35%. 18 out of 31 had a greater than 30% reduction in pain, and 12 of 31 patients had clinically meaningful palliation of pain, so good results here with regards to quality of life and pain. And also safety.

ERA 223

So, November 30th we’ll talk about ERA 223. So this is a randomized double-blind, placebo-controlled, multi-national, multi-center Phase 3 study that is looking that is examining patients with CRPC with bone mets, and the patients were asymptomatic or mildly symptomatic. They were chemo-naïve, and it included roughly 800 patients, and they were randomized in a 1:1 ratio to either radium plus abi and prednisone versus placebo and abi and prednisone.

Important Drug Warning

So November 30th, 2017, I think I was in Chicago for – – and this red box warning comes out.

November 30, 2017

The Independent Data Monitoring Committee reported an increased incidence of deaths, and fractures, and they required that the study be unblinded. So, there’s very limited information, but they did report that the incidence of fractures was 24% in the treated arm versus 7% in the placebo arm, and deaths were 27% versus 20%.

ERA 223

So the full analysis isn’t complete, and I don’t think we’ll see the data form that for at least a few months, but the current recommendations are not to treat anyone with radium plus abiraterone, and for those that were treated, to follow them closely. Interestingly none of these—all of the doses of radium were actually completed much earlier so this was during the follow up phase.

They also did announce that there was some preliminary that indicated that denosumab or bisphosphonates may minimize the risk of fractures, but again that’s all we have, and we don’t have more data on that.

Stratification

In that study, the patients are stratified based on geography, their use of denosumab/bisphosphonates, and total alk phos. So, it will be interesting to see that data to see if geography played a role in some of this, and also to see how denosumab and these bone protective agents actually helped.

Failure is success if we learn from it.

So failure is success if we learn from it, and I think that’s true. And we’ve seen a lot of quotes about failure all the time, and I think, you know, we can’t take failure as a reason to stop trying or just totally pivot 180 degrees.

A Successful Failure

Chuck Ryan wrote an interesting blog post on – -Today recently about this trial, and talking about equating it to the Apollo 13 mission, and for those of you familiar with that, it went up, the mission was to land on the moon. There was an explosion due to an oxygen tank that exploded because of an uncovered wire. Obviously, that is catastrophic when you’re in space, but they actually figured out away to get back to earth safely, so that was a successful failure. So, I think this sort of just puts things in perspective that we don’t need—shouldn’t overreact.

Hypothesis

I think we need to look at things carefully, and we need access to that data to really dissect what are the areas that went wrong, what are the, you know, what is it telling us? That is why we do these clinical trials, and that is why we need access to this data to really see where we go from here, but in the meantime, I think it is kind of fun to hypothesize with regards to why this might have happened, and when I talk about it with Neal, and Dave, and various other people, I think one possible hypothesis is that maybe there is a flare response. We do know there is a flare response with abiraterone. So, in the Phase 3 trial looking at abi and prednisone, there was a flare response, and they saw a discordant bone scan in 12 of 23 patients, so discordant in the fact that the bone scans looked worse, but the PSA went down greater than 50%, and those bone scans that looked worse, 80% of those scans actually improved on follow-up. So flare was seen in 43% of responding patients. And this goes back to Dr. Reiter’s point, that bone scans aren’t very good, and yet we incorporate them into all of our clinical trials.

McKay RR

This is an example of flare published in 2016, but again we have seen this for years, but you take a case at baseline and you look at him at three months, and you look at them at six months, and you see a sternal lesion that will look hotter, a little worse at that three-month scan, and it sort of stabilizes. And again oftentimes you see this, especially in breast cancer patients if they have osteolytic disease. They often get treated. The bone scans look terrible, and they stabilize or look better. And again, that is most likely bony reparative response to these lesions being treated.

Radium 223 Flare

Radium 223, we’re learning more about Radium 223 and how it works, and how it reacts on imaging, and there was a recent study published in 2017 that talks about bone flare and that bone flare is pain flare and/or radiological flare. So bone pain increased in 27% of those patients. It decreased in 49%, and they saw an increased number of lesions in 26%. 74% were stable at three months.

Combination vs Layering?

So the big question is, maybe there is a difference between combination versus layering, so if you look at the expanded access trial, you look at Neal’s ERADICATE trial, maybe the difference here is combination versus layering. In ERA 223 these patients were started on abiraterone with Radium 223 within a three-day window simultaneously. In ERADICATE, one-third of patients I believe were started on abiraterone at least a month before and two-thirds of patients, two-thirds of the patients were actually started on abi 60 days at least 60 days before they were started in Radium. So again, maybe that’s one of the differences. Maybe you sort of clear that flare response in the beginning, and then you add the radium, and that is why we’re seeing those improved survival rates, when it’s layered as opposed to combination. Again, we don’t know this for sure, but just kind of fun to speculate.

PEACE III

PEACE III is another trial. It’s a randomized multi-center, phase III trial comparing enza versus enza plus Radium 223. Very similar to the ERA 223 trial, so that will be interesting to see what that reports, and that is scheduled to be completed in November 2019.

Conclusions

So quickly, conclusions.

Donald Rumsfeld

You know, when this quote first went up or was mentioned years ago, it was confusing, and I know a lot of us laughed, but the more you think about it actually it kind of makes a lot of sense, and “There are known knows, these are things that we know that we know. “There are known unknowns, that is to say there are things that we know that we don’t know, but there are also unknown unknowns, there are things that we don’t know we don’t know.” That’s mind-boggling right, and it actually makes a lot of sense.

Every day I’m reminded that there are so many things that I don’t know I don’t know, and it’s kind of –it makes life a little more interesting, so kudos to Donald Rumsfeld for being able to articulate that on the spot.

Radium 223

So anyway, “Radium 223:” I think the personal ad is still out, “Enjoy bone seeking journeys and long walks on hydroxyapatite crystals. I help patients live longer while promoting safety. Seeking like minded partner who likes bone as well but ideally could treat soft tissues as well,” because that would be a marriage made in Heaven. I like that there as well.

Raoul S. Concepcion, MD, presented “Immunotherapy 101 for the Urologist” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado

How to cite: Concepcion, Raoul S. “Immunotherapy 101 for the Urologist” January 27, 2018. Accessed [date today]. https://grandroundsinurology.com/Immunotherapy-101-for-the-Urologist/

Summary:

Raoul S. Concepcion, MD, summarizes the mechanism of action behind the immune response to cancer. He also provides an update on the current and emerging immunotherapies for cancer treatment, including vaccines, checkpoint inhibitors, CAR T-cell therapies, viral vectors, and adoptive cell therapy.

Immunotherapy 101 for the Urologist – Transcript

Click on slide to expand

Immunotherapy 101:  A Guide for Urologists

Yeah, this is pretty easy, so I’m going to take a little bit of a different pathway here. We’re going to talk—this is going to be more of a didactic lecture. What I thought I would do is level set for the audience where we stand with some basics as it relates to immunology and immunotherapy, which as we all know, is really going to be sort of this burgeoning explosion of new therapy. I’ve entitled this lecture Immunotherapy 101: a Guide for the Urologist.

Disclosures

So these are my disclosures.

Objectives

And so the objectives of this talk is going to be to explain and define the mechanism of action behind the immune response to cancer, and again we’re going to talk really some basics about what the immune system does and better define the types of immunotherapy current and emerging used for cancer treatment.

Immunotherapy/Hormonal Therapy

This slide really was just data that’s 2012, but basically this is really related to prostate cancer tumor cells, and so we know the canonical mechanism as was described earlier. We know it’s all driven by the androgen receptor, which involves binding of the androgen ligand to the receptor result—then you get nuclear translocation of the receptor ligand complex. DNA binding transcription and translation, so when we look at the current therapies that are available, we know that historically speaking, as we all know hormonal therapy has been sort of the foundation, and now with some of these secondary hormonal agents, including abiraterone, this was the original MDV3100, which we now know is enzalutamide, and then we have targeted therapies, cytotoxic therapies, which were your traditional chemotherapeutic agents. Then we also know because of the potential for prostate cancer to metastasize, we have bone targeted therapy, which involves not only treatment, but as well as attempts since we know that androgen deprivation therapy does result in bone mineral density loss, we also get some bone targeted agents that are available to not only prevent SRE, but also increase bone mineral density. But clearly what we know now, and again this has really been over the past few years has exploded.

Breakthrough of the Year 2013

And the one as this slide shows that was initially approved was sipuleucel T, which we know is an autologous immunotherapy, but since 2013, and again this continues to almost change on a monthly or weekly basis. This is all about immunotherapy. What I thought I would do is sort of level set for everybody sort of the basics of the immune response.

William Coley

So this is William Coley. So, Coley was a surgeon in New York. He was a general surgeon. He actually had a very specialized niche. I don’t know of anybody that does this now, but he only really took care of sarcomas, and what he observed in the late 1800s, was that there was a patient who had a metastatic sarcoma site to his neck that developed a severe skin infection and it actually had spontaneous resolution of the tumor.

So, Coley postulated that possibly this was related to this inflammatory response. So what Coley did, and really this is kind of one of the true first clinical scientists, what he did is he basically injected tumor sites, most of them were inoperable sarcomas that were metastatic. He injected attenuated a mixture of strep pyogenes and another bacteria, which we now know is soracea. He basically attenuated them. He heat killed them, and he injected these directly into the tumor sites to set up this basically immune response, and so actually this was sort of the—sort of one of the first uses of immunotherapy, but it was a direct injection of hopes of creating this immune response.

The Long Pursued Goal of Engaging an Effective Antitumor Immune Response Has Recently Come Within Reach

So many of you have probably seen variations of this timeline, so Coley did his first work in the late 1800s. Then there was sort of this lack of anything, but then back in the 60s, we started using BCG. Rosenberg then started doing a lot of work at NIH with Interferon IL2, but as you can see here, as we all know the first cellular immunotherapy approved for prostate cancer was sipuleucel T in April of 2010, and since then we have had a number of different immunotherapies approved, and again this number continues to increase, and I predict will basically continue to go on for the next couple of years.

The Immune System Has:  Innate – Adaptive

So when we talk about the immune system, you really have to talk about two basic concepts. You talk about an innate immune system, and the adaptive immune system. So the innate system is non-specific, you don’t need antigen presentation, it doesn’t have memory, the time frame is immediate course of action. The duration is transient, and the cell types really are macrophages, macrophages, dendritic cells, natural killer cells and neutrophils.

The adaptive system, which is really again I think more important, it is very specific. It does require antigen stimulation. It does generate memory. It’s slowly developing, and you have a lifelong duration, and its main cells really are T cells and B cells.

Cells of the Innate Immune System

So again, the cells of the innate system, you have the neutrophils, which are basically result in phagocytosis and debris clean-up. It secretes cytokines that call in other innate immune cells. You have these dendritic cells, which are very important to understand, especially with the current immunotherapy that is approved of sipuleucel T, and these are the antigen presenting cells. You have macrophages, and you also have these natural killer cells.

Cells of the Adaptive Immune System

When you look at the adaptive immune system, this is really based upon two types you have basically your B lymphocytes, which are responsible for specific antibody production that are generated against extracellular epitopes or microbes with specific antigen. This is again when we took immunology back in college, back in medical school, this was sort of that lock and key effect, so it results in specific antibody production, you get neutralization, lysis and phagocytosis.

The T-cell response really involves these antigen-presenting cells, uptake of an antigen, presentation and then activation of these really specific T-cells that again will have long-term memory.

Initiation of Immune Response:  Key Cells

So the initiation of this is really and this is courtesy of our folks from Dendreon, is that you have these antigen-presenting cells. They take up the antigen. You get presentation of these antigen fragments for sipuleucel T, it’s actually against the antigen that is used to stimulate this activation is prostatic acid phosphatase. This actually happens in lymphoid organs. Then you have these activated T-cells, then you have these effector cells that basically result in cell death. These effector cells again are targeted. You get up regulation, and again this is antigen-specific.

Releasing the Power of T-Cells:  CTLA-4 and PD-1 Blockade

So, when you look at this at the receptor level, and this is probably the most important slide, because you hear these terms all of the time, you hear CTLA4 PD-1 Blockade. So again, what you have here, the key cell here is the T-cell. So as we showed, this priming phase is really a two-step process.

So what you have in these dendritic cells that have taken up the antigen, they present through a major histocompatibility receptor. They basically have this presentation of the specific antigen, which binds to the T cell receptor. Then you also have these other basic proteins, ignore this for a second, but you have these other basic proteins that when they also bind to certain receptors you then get activation of these T cells that become very specific. So this is sort of the priming of these T cells, and then on the effector side what tends to happen is that again you have an antigen that’s been targeted. You get binding of the activated receptor to the antigen on the cancer cell. But because of this binding over here to CD20A receptor, you get this whole up regulation. But what happens is that we have these natural proteins, these checkpoint inhibitors, and so what happens is that on the dendritic cell these checkpoint proteins when it binds to CTLA4 what that results in is basically an inhibition of the T cells. On the effector side you then have PD1 and PDL1 so if you get binding of PDL1 to PD1 then you get down regulation and it affects the—it basically knocks out the effector phase. So this is really a very important concept, and it is important to understand where this actually takes place.

Rationale for Immunotherapy Combination with Immune Checkpoint Inhibitors

So again this rationale for immunotherapy combination with immune checkpoint inhibitors, is that you have the checkpoint inhibitors, these anti-PD1, PDL1, CTLA4 inhibitors, which really result if you block them if you block this interaction, you then release the effect and you get up regulation of all of these effector T cells. If you block PD1 or PDL1, you then block this interaction and what you get is what normally results in a negative regulatory effect.

Critical Link Between Innate and Adaptive Immunity

So again, this is sort of these critical links between the innate and adaptive immunity. This is probably one of the most—this is a great little video that I thought I would just show. This really talks about this PD1, PDL1 interaction.

[Video]

I thought that was one of the greatest little videos that I’ve ever seen.

Radiation Driven Immunotherapy (RDI)

So again, these cancer cells to put it simply when they express PDL1 that binds to this receptor, that is sort of their cloaking mechanism, if you will, at the effector side, so binding of PDL1 or binding of the receptor basically takes that out and allows the T cell immunity to sort of take place.

So another area of immunotherapy is what we call radiation driven immunotherapy. We believe that basically ionizing radiation results in sort of this double stranded DNA breaks that are more difficult for the body to repair.

Radiation Driven Immunotherapy (RDI)

That sounds very simple, but there is probably a lot more going on here so again we get this ionizing radiation. We think it results in these sort of double-stranded DNA breaks, which are more difficult to repair than single-stranded breaks, but probably at the same time you get this release of all of these other molecules cytokines, receptors, adhesion molecules that result in this massive stimulation of the immune system.

Radiation Driven Immunotherapy (RDI)

So again, the most dramatic clinical effect, outcome of this, when distant tumor masses regress is sort of known as the abscopal effect, and I think Dr. Koo may be talking a little bit about this in terms of the Radium-223, which is obviously a systemic alpha emitting particle, and how it could be used essentially with other combination therapies.

Types of Cancer Immunotherapy

When we think about cancer immunotherapy and again this is sort of a generalized way that I think people ought to be looking at this, so we have vaccines, so we have checkpoint inhibitors, there was some attempt at oncolytic viral therapies, using viral vectors, and then something new, which we’ll touch base briefly, which is becoming more and more important, is the adoptive cell therapy.

Active Cellular Immunotherapy (Sipuleucel T)

So we know that active cellular immunotherapy though again the one that is approved, and the only one that is approved for prostate cancer is sipuleucel T which was approved in April of 2010, I’m sure many of you have had personal experience, know about sipuleucel T, but really what it involves, it involves apheresis, where you pull out these dendritic cells, these antigen-presenting cells, you incubate them with a fused molecule GMCSF and basically you target prostatic acid phosphatase. You get up regulation. This process takes place ex vivo. It’s shipped back to the provider’s office, and then it is infused. As all of you know, sipuleucel T is approved and does have a survival benefit with recommendations by many of the guidelines that David talked about.

Oncolytic viruses

Again, there were other attempts to use viral vectors that have been attenuated. We know that native or engineered viruses that target, infest and kill cancer cells and unfortunately the one oncolytic viral therapy basically had a negative read out last year.

Immune checkpoint inhibitors

We’ve talked a little bit about these checkpoint inhibitors and again I think what is important to know is that the CTLA4s really target right here in terms of the priming effect, and then as we talked about in the video, the anti-PD1s and PDL1s really are at the effector side.

CAR T-Cell

Now, this new area, which again is getting a lot of press, and there’s a lot of companies that are involved in CAR T-cell therapy. There’s Juno, there’s Gilead, Kite, Novartis, is this concept of chimeric antigen receptors.

Adoptive cell therapy

Really what this is is the incorporation of an immunoglobulin variable domain which is fused to a T-cell receptor. It emits the need of antigen expressing mechanism to be functional.

Building a CAR

This is how you build a CAR T. Basically, you have a structurally a single chain antibody that is attached to a T cell or a modified T cell receptor and it targets a native tumor antigen. You then have incorporation of some other stimulatory molecules.

Building a CAR Illustration

This is sort of how it looks like.

Process of CAR T-cell Therapy

And really how it works is you get a pheresis, you get up regulation of the patient’s T-cells and then you create these chimeric antigen receptors, and then it gets reinfused.

New and Improved CARs

And we have had multiple generations, and again, looking at some various different types, but it all involves basically incorporation of an antibody that is fused to the T-cell receptors.

Immune-Related AEs With Immunotherapy

There are some immune-related adverse events with immunotherapy, and again, as we see more and more of these because they are going to be used, they are used right now there’s many of them involved obviously in the bladder cancer space, but you know everything all of these immunotherapies are rapidly expanding with rapid approvals, so we get some dermatitis reactions, some ophthalmologic, some endocrine, and the list and, so again, as we choose, especially the medical oncologists, are really adept at managing these, but as urologists, as we attempt to move more and more of these into our practices, we really, like anything else, need to beware of the side effect profiles with all of these therapies.

Conclusion

So in conclusion, understanding of the immune system is critical as we develop newer therapies that target tumor cell antigens. Checkpoint inhibitors, especially in combination with other therapeutic modalities, represent new opportunities. Ongoing clinical trials will still be needed, especially utilizing and developing predicted biomarkers. Thank you.

CRAWFORD:  Wow, you are smart.

L. Michael Glode, MD, FACP, FASCO, presented “The Role of Targeting DNA Repair with PARP” at the International Prostate Cancer Update on January 27, 2018 in Beaver Creek, Colorado

How to cite: Glode, L. Michael . “The Role of Targeting DNA Repair with PARP” January 27, 2018. Accessed. [date accessed] https://grandroundsinurology.com/The-Role-of-Targeting-DNA-Repair-with-PARP/

Summary:

L. Michael Glode, MD, FACP, FASCO, discusses the mechanism of action of PARP, the basic science behind Synthetic Lethal mutations, clinical trials for PARP inhibition in prostate cancer, and the importance of testing for DNA repair mutations.

The Role of Targeting DNA Repair with PARP – Transcript

Click on slide to expand

Lecture Outline

All right. So the questions are what is PARP anyway? How does it work? Basic science of synthetic lethal mutations, and does it matter in the clinic? And what about prostate cancer?

Poly ADP Ribose Polymerase

This is a really interesting story. As most of you know, in the last 20 years or so we’ve had tyrosine kinase inhibitors and they add phosphate groups to tyrosine on proteins that making negative charge, and thus altering function of the protein; dimerization can occur and so forth. Well, it turns out that Poly ADP Ribose Polymerase, PARP, does much the same thing, adding negative charges, phosphate groups, but rather than just a single phosphate, multiple phosphates. As with TK’s there is a target protein, and it can be histones and DNA or for example diphtheria toxin A chain which is a PARP that ADP ribosylates Elongation Factor 2, and that has been an area of interest of mine. The key thing to remember is how potent this can be, so via this one PARP enzyme, DTA, a single molecule of diphtheria toxin can kill a cell. So this can be a very potent effect, but you can start adding more and more chains and eventually get more and more negative charges and that can affect the histone interaction, and recruit other function proteins to DNA repair areas. So this is called parylation, and it’s negative charges leading to structural changes in protein.

Mechanism of action of PARP1 – Synthetic lethality

Now, in the situation of using it in cancer therapy, and we’re going to talk a lot about BRCA1 and 2 in a little bit here, the first thing we want to go through is synthetic lethality, and this means that you have, let’s say this is BRCA1 or 2, and it does not cause cell death, but it does lead to cancer because you get mutations. If you had another mutation in a DNA repair pathway, the cell could still survive, but if you get both of these mutated, or knocked out in the case of BRCA1, and now you add a PARP inhibitor, it leads to cell death. So this is how that looks. You have some patient with any number of DNA repair pathways, and we’ll look at those in a second, and they have mutations in the intrinsic germline or a somatic mutation, their tumor has developed a mutation in DNA repair, and this is PARP and it has zinc fingers that can recognize a single strand break, and attach to the histones associated with this protein and begin doing its enzymatic thing. First thing that happens is it refolds itself, etc., and brings in the catalytic domain to start doing this parylation that we just talked about using NAD as the substrate and adding ADP riboses to this, and that recruits other factors and you start getting repair of the DNA. The PARP1 inhibitors actually trap this so that you can’t go through this pathway and re-establish the uninhibited PARP. So the PARP inhibitors sort of trap this in this configuration and it adds the second mutation that leads to cell death. So that is how PARP inhibitors work.

DNA Repair Mutational Landscape in Prostate Cancer

So how does this relate to cancer in general, and prostate cancer in particular? Well, we all know that there are lots of mutations that occur in all cancers, and they can be characterized as repair pathways, as double-strand breaks rather insertions, deletions, different types of damage with different types of repair pathways, and base excision repair is where you take out the base that is mutated and put a new one in. The double strand mutations can occur after a single-strand mutation if you don’t repair things. So, this is a nasty thing that starts happening, and there are a whole series of genes related to DNA repair, and if you have germline mutations in any of these genes, you are at increased risk. I found this to be incredibly interesting. So they’ve looked at in this New England Journal article, published two years ago, 692 men with metastatic prostate cancer, and 12% of those had germline mutations as opposed to only 5% or so with localized prostate cancer. So this means that these people with germline mutations who develop prostate cancer, their cancer is worse and metastasizes more early. You’re walking around with 53,000 people looked at and 2.7% of us have a germline mutation in one of these many DNA repair pathways.

PARP inhibitors

So the PARP inhibitors were developed, as I showed you, to interrupt this pathway. Here is the simple version of what we just looked at, the normal PARP1 function, single-strand break. You have parylation events that lead to repair. The PARP inhibitors prevent that repair. There are a number of inhibitors, small molecules, that have been developed to work this way, and we will look at olaparib as the one that has been evaluated in prostate cancer. Each PARP inhibitor has a different level of PARP-trapping potency. And all of them are being looked at in prostate cancer.

TOPARP study

So this TOPARP study had 49 patients with metastatic prostate cancer who had been treated with at least one of the second-generation hormones, hormone blockers that you’ve heard about, and were also docetaxel pre-treated. They then had—they treated everybody in these unselected patients but looked at in retrospect what the tumors had in the way of DNA repair mutations. So in their genomic analysis of their prospectively obtained tumor samples, 16 of the patients had mutations in the DNA repair pathway, and 33 had no such mutations, Then you looked at what was the response rate, and 14 of the 16 patients who had the repair pathway mutations responded, as opposed to only 2 of the 33 patients who didn’t have these mutations. So, this is personalized therapy at its best, and that’s why this has generated a lot of excitement.

The New England Journal

These are the data sort of spread out, and looking up here this is the radiographic progression-free survival in the patients who had the repair pathway mutation versus the patients who did not, and this is their overall survival. So a substantial difference, and because of this study, olaparib was granted breakthrough therapy designation by the FDA in 2016. However, as best I can tell it is still not approved for treatment so it is probably not covered by third parties. This is the different mutations that we looked at in that pie diagram. They were all over the map, and these are the two patients that responded that did not have such repair pathways defects.

DNA damage response mutations are predictive in a % of many cancers – “personalized”

So this is outside of prostate cancer areas of interest. This is an article that was published just a few days ago in pancreas cancer patients, where the same sort of analysis is recurring. These are the carriers of a DNA repair pathway mutation versus the non-carriers with very significant P values. This is in metastatic breast cancer, where in August of last year germline BRCA mutation patients are now approved for olaparib in treating metastatic breast cancer. And this is the same drug in platinum-sensitive relapsed ovarian cancer, where it has been approved, and a recent study showing that you can prolong the survival of platinum pre-treated patients in this situation.

Clinical assessment of PARP1 synthetic lethality

So the clinical assessment of PARP inhibitor synthetic lethality, which we’ve talked about, is now important in breast cancer, pancreatic cancer, prostate cancer, and it’s approved in ovarian and breast cancer, and substantial fractions of these patients have ongoing clinical trials of various sorts. There have been FDA approvals in a few of the other diseases.

PARP Inhibition in Prostate Cancer

PARP inhibition in prostate cancer has breakthrough designation. It will be, if they go with the usual kind of language, indicated for patients who have metastatic disease who have either BRCA1 or 2 or ATM mutations, either in the tumor or germ line, and have received a prior taxane and at least one second generation hormonal therapy. This is under expedited review. The dose is 300 mg twice a day given orally. And the side effects are fairly significant. In one of the studies, not in prostate cancer, 11% of patients stopped taking it because of toxicity. Fatigue and asthenia in as high as 70% of patients. Nausea is frequent. Vomiting less frequent. Low white counts and anemia, and then rarely this can induce myelodysplastic syndrome or acute myelogenous leukemia, pneumonitis and fetal harm is expected but hasn’t been shown. So there are a number of clinical trials targeting the DNA damage response and being developed with all of those different drugs that I showed you.

Ongoing Trials of PARP Inhibitor

This is from Dan Petrylak’s slide set. This is olaparib, the one that is the farthest along in development, and these are different trials that are underway with the NCI designations over here. This is rucaparib in hormone refractory DNA repair deficient metastatic prostate cancer, and another trial of that. This is another inhibitor.

Combination Trials

Here are three more trials with olaparib in different settings combining it with other drugs, because in theory if you have DNA breaks, and then you add this drug to an alkylating agent or even platinum for example, you should be able to accentuate the activity of this drug combination.

Conclusions

In conclusion, PARP inhibitors or platinums have significant activity in patients with a variety of cancers. These responses are much higher with germline or somatic DNA repair mutations, and this brings into clinical use the synthetic lethal interactions that were hypothesized over 50 years ago, and we now have clinical applicability of this approach to treating cancer. You can combine this with other DNA damaging agents. Testing for DNA repair mutations in germline or tumor tissue is becoming more important. That’s going to be covered tomorrow. When do you do it? How much are the costs of doing that? And then when you do the cost analysis, you have to ask what is the benefit to doing this if it costs a fair amount to do the analysis of DNA repair mutations, but you save giving patients a drug that is going to be ineffective? You may actually save money by doing the repair mutation analysis first. And then there are possible implications for checkpoint inhibitors that I won’t go into, but when you have BRCA or ATM mutations, you get a phenotype of different mutations downstream from that which indicates what is called “BRCAness”, and those patients are the ones that have a much higher burden of mutations, and that in turn leads in some studies to more abnormal proteins being released and increased sensitivity to the checkpoint inhibitors, which as you know in diseases like melanoma have been dramatic, and we are hoping to get there in prostate cancer one day.