California Archives

Treating BPH: Comparing Treatment Modalities

Posted by Michael E. Albo, MD | May 2022

Michael E. Albo, MD, Vice Chair of the Department of Urology at the University of California, San Diego, compares the efficacy, safety, and considerations for a variety of treatment options—both traditional surgical and newer, minimally-invasive therapies—for patients with benign prostatic hyperplasia (BPH) causing lower urinary tract symptoms (LUTS). He begins by outlining the surgical management of LUTS attributed to BPH before discussing the goals and selection of treatment. He explains the patient and urologist perspectives in terms of evaluating minimally invasive therapies before summarizing the various treatment options as a whole. The first are resection treatments, including transurethral resection of the prostate (TURP) (which Dr. Albo calls “the gold standard”) and transurethral incision of the prostate (TUIP). Next he describes enucleation technologies, including simple prostatectomy, laser enucleation of the prostate (using holmium [HoLEP] or thulium [ThuLEP] lasers), and bipolar enucleation. Dr. Albo explains that while simple prostatectomy should be considered only for patients with large to very large prostates, laser enucleation options are size-independent options for the treatment of LUTs/BPH; additionally, the HoLEP and ThuLEP options have more favorable perioperative safety and he advises these be considered as treatment options in patients at higher risk of bleeding. Dr. Albo then addresses vaporization procedures, including bipolar transurethral vaporization of the prostate (TUVP) and photoselective laser vaporization of the prostate (PVP), explaining that PVP is likely safe for patients on anticoagulants. At this juncture he turns to the minimally-invasive prostatic urethral lift (PUL), citing studies showing this is less effective than TURP but with similar quality of life improvements. Dr. Albo makes the point that trials need to better evaluate minimally invasive interventions in terms of whether patients are able to discontinue medication and therefore whether that intervention can be considered successful. He discusses water vapor thermal therapy (WVTT), citing data supporting the preservation of erectile and ejaculatory function and five-year data showing sustained changes in International Prostate Symptom Score (IPSS) and Qmax. Robotic waterjet treatment (RWT) has been shown to be effective and safe, with the main drawback being bleeding; Dr. Albo predicts that, while more needs to be learned as far as RWT for larger prostates, this procedure could be game-changing. He mentions two additional procedures, transurethral microwave therapy (TUMT) and prostate artery embolization (PAE) (which currently is not recommended outside the context of clinical trials) as well as an investigational treatment with nitinol struts to remodel the bladder neck. He concludes by asserting that the field has come a long way in terms of the sophistication of the surgical treatment algorithm, emphasizing the importance of a discussion with the patient in terms of side effects, the availability of technology at the institution, and the surgeon’s skill level in the decision-making process.

Non-Muscle Invasive Bladder Cancer: Guidelines-Based Approach

Posted by Raj S. Pruthi, MD, MHA, FACS | May 2022

Raj S. Pruthi, MD, MHA, FACS, Professor in the Department of Urology at the University of California, San Francisco, reviews the American Urological Association (AUA)-Society of Urologic Oncology (SUO) guidelines on diagnosing and treating non-muscle invasive bladder cancer (NMIBC). He begins with some statistics, relating that in 2017, there were approximately 79,000 new cases of bladder cancer, 16,800 deaths, and greater than 500,000 survivors. Dr. Pruthi observes that bladder cancer is a disease of older individuals, and he predicts that the population of bladder cancer patients will increase as the population ages. He then highlights key facts about NMIBC, explaining that most patients recur, some progress, and the ability to predict recurrence and progression is based on patient-specific disease characteristics. Dr. Pruthi introduces the 2016 AUA/SUO guidelines, noting that the panel featured a patient advocate. He goes over the guidelines point by point, starting with diagnosis. Dr. Pruthi underscores the importance of performing a complete visual transurethral resection of bladder tumor (TURBT) at initial diagnosis, explaining that incomplete TURBT is a contributing factor to early recurrences. He notes that risk calculators for NMIBC are limited by lack of applicability to current populations, and also that no study has evaluated the effectiveness of urinary biomarkers to decrease mortality or improve outcomes compared with standard diagnostic methods. When discussing guidelines around treatment, Dr. Pruthi emphasizes the importance of re-resecting T1 disease since understaging occurs in about 30% of cases and patients with residual T1 (after presumed complete resection) have up to an 80% chance of progression. He also discusses guidelines around BCG administration and BCG relapse. Dr. Pruthi then looks at cystectomy, arguing that waiting until progression to muscle invasion may prove fatal. He concludes by discussing guidelines around follow up.

Industry Perspective: AR-V7 Testing for Men with Advanced Stage Prostate Cancer

Posted by Daniel Shoskes, MD, FRCSC | May 2022

Daniel Shoskes, MD, FRCSC, Medical Director in Medical Affairs for Urologic Oncology at Exact Sciences, and Emeritus Professor of Urology at the Cleveland Clinic, discusses AR-V7 testing for men with metastatic castrate-resistant prostate cancer (mCRPC). He begins by noting that mCRPC cannot be cured, but patients with mCRPC often benefit from multiple lines of sequential therapy. Dr. Shoskes explains that when one therapy fails, choosing the next therapy can often be difficult, in part because patients often prefer AR-targeted therapy over taxanes due to the less burdensome side effect profile of AR-targeted therapies. As a result, even though secondary AR-targeted therapy is only effective 22-46% of the time, AR-targeted therapies are administered back-to-back up to 60% of the time. Dr. Shoskes observes that AR variants are a common cause of AR-targeted therapy resistance, and of those variants, AR-V7 is one of the most common and best understood. He defines AR-V7 as a splice variant of the androgen receptor protein which is active without the ligand binding domain, making it resistant to abiraterone, enzalutamide, and apalutamide. Dr. Shoskes then introduces the Oncotype DX AR-V7 Nucleus Detect assay, which he argues can help clinicians quickly direct their mCRPC patients toward the right treatment. He explains that the Nucleus Detect assay detects the AR-V7 protein in the nucleus of circulating tumor cells, is predictive of resistance to AR-targeted therapies, provides easy-to-interpret and actionable results, and only requires a simple blood draw. Dr. Shoskes highlights that the Nucleus Detect assay has been validated in three independent studies, all of which found that it to be predictive of non-response to AR-targeted therapy. He concludes by discussing outcomes, noting that in the validation studies, AR-V7+ patients experienced a 76% survival benefit from being placed on taxane therapy versus AR-targeted therapy.

Updates in Treatment Using ADT and Anti-Androgens

Posted by E. David Crawford, MD | May 2022

E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, discusses the state of androgen deprivation therapy (ADT) and anti-androgens as treatment methods for prostate cancer (PCa). He describes the mechanism of action of anti-androgens, stating that while they should be the best treatment for prostate cancer based on their ability to block tumor development without lowering testosterone levels, anti-androgens have some flaws. Dr. Crawford goes over the history of anti-androgens, beginning with Huggins demonstrating the efficacy of androgen ablation in 1941 and ending with apalutamide’s demonstrated efficacy in 2018. He suggests that anti-androgens are the backbone of treatment. Dr. Crawford discusses the safety of novel hormonal therapies based on data from PROSPER, SPARTAN, and ARAMIS that show adverse effects leading to death and discontinuation never increased by more than 8% relative to placebos. He then reviews discussions from the RADAR V group on how the transitional state from biochemically recurrent disease to advanced disease needs to be identified and managed in order to create better outcomes. Dr. Crawford also discusses the PEACE-1 trial which emphasized that combination therapy is key to treating specific forms of disease, as well as the SWOG S1216 trial which found that overall survival in the ADT treatment arm did not surpass the control arm’s overall survival of 70 months. Dr. Crawford concludes that anti-androgens are here to stay.

High Intensity Focused Ultrasound for Prostate Cancer

Posted by Hao G. Nguyen, MD, PhD | May 2022

Hao G. Nguyen, MD, PhD, Associate Professor of Urology at the University of California, San Francisco, reviews high intensity focused ultrasound (HIFU) for prostate cancer, discussing its basic principles, historical development, current role, and outcomes. He begins by describing HIFU as a non-invasive approach that uses precisely delivered ultrasound energy to a deep tumor necrosis while minimizing side effects, specifying that its success depends on careful patient selection and lifetime surveillance. Dr. Nguyen outlines the history of HIFU from the first prostate cancer treatment with HIFU at Lyon University Hospital in 1993, through 2022. He reviews the NCCN, AUA/ASTRO/SUO, EAU, and DGUS3 guidelines, all of which suggest that HIFU is an option for prostate cancer treatment, but not yet standard care. Dr. Nguyen discusses how focal therapy can work to fill an important treatment gap in prostate cancer, between active surveillance and radical therapy, due to the oncological control with minimal side effects that HIFU provides. He summarizes data on upgrade-free survival during active surveillance that found high rates of overall survival, prostate cancer specific survival and metastases-free survival. Dr. Nguyen also considers data on the role of focal therapy in active surveillance which demonstrates that 70% of FT candidates remain favorable for hemiablation based on biopsy. He then discusses four ways that HIFU can fail: the heat-sink effect wherein cancer vessels wash heat in or away; the margin effect which signals a missed satellite cancer area; the staging effect wherein micromets or clinically significant cancer is missed; and the field effect which is the progression of low-risk cancer or a pre-cancerous area. Dr. Nguyen concludes that HIFU has promising oncological data and could be shown to be an effective option for patients who don’t want active surveillance or radical therapy.