2021 Archives

Changing Paradigm in Testosterone Therapy Treatment Options

Posted by Mohit Khera, MD, MBA, MPH | Jan 2022

Mohit Khera, MD, MBA, MPH, Professor of Urology and Director of the Laboratory for Andrology Research at the McNair Medical Institute at Baylor College of Medicine in Houston, Texas, discusses testosterone therapy, focusing on four key topics: oral testosterone, testosterone and COVID-19, testosterone and prostate cancer, and lifestyle modification. Dr. Khera provides a historical context for oral testosterone treatments, noting that the US has only recently seen expansion of this option. He describes the inTUne study which showed that 7% of patients may increase or start hypertension medication while on a testosterone oral therapy, but that overall patients experience a lower rate of erythrocytosis when compared with those receiving injectable and topical forms of testosterone. Dr. Khera then reviews several studies examining the relationship between COVID-19 and testosterone. Early studies showed men were more severely affected by COVID-19 than women. Paradoxically, low serum testosterone may be protective against acquiring COVID-19, but the same low serum testosterone can also result in a more severe outcome if that same patient acquires COVID-19. Additionally, COVID-19 also directly impacts the testicles in that serum testosterone levels significantly decrease from their pre-COVID-19 levels. Transitioning to prostate cancer, Dr. Khera describes the paradigm shift over the past 15 years, with physicians previously viewing testosterone as dangerous to now seeing it as protective. He illustrates the point with a prostate saturation model that shows the non-linear relationship between testosterone, PSA, and prostate size. Dr. Khera then considers treatment options with high levels of testosterone, such as bipolar androgen therapy, that have shown promising results. He concludes with a review of lifestyle modifications that can also improve testosterone levels, such as weight loss, sleep, and varicocele.

Use of MRI-Targeting Increases Overdiagnosis and Overtreatment

Posted by Andrew J. Vickers, PhD | Jan 2022

Andrew J. Vickers, PhD, Attending Research Methodologist at Memorial Sloan Kettering Cancer Center in New York City, asserts that the current diagnostic use of MRI-targeting leads to overdiagnosis and overtreatment. He begins by stating that methods of detection such as systematic biopsies and measuring prostate-specific antigen (PSA) don’t tend to lead to underdiagnosis and undertreatment. To illustrate the reasons MRI-targeting leads to overdiagnosis and overtreatment, he displays data showing that in MRI-targeted biopsy the method of grading the core samples leads to higher grading of overall disease. Dr. Vickers points out that Gleason grade is not an inherent property of a tumor, but is instead a surrogate outcome. He then illustrates that biochemical recurrence (BCR) risk and risk of death for high-grade cancer on surgical pathology is dramatically reduced for clinically low-risk patients. Dr. Vickers cites the PRECISION trial which indicated that the MRI-targeted biopsies found far fewer low-grade cancers and more high-grade cancers, but the overall number of cancers identified was essentially the same. Dr. Vickers asserts that these results are consistent with a scenario whereby the technique simply characterized some of the low-grade cancers as high-grade. He then cites another study during which patients had both a systematic and an MRI-targeted biopsy; the MRI targeting identified more cancers that, in turn, led to more treatment. Dr. Vickers suggests this is problematic and opines that urologists do not need to find high-grade cancer in men with low-grade cancer on systematic biopsy. He supports his assertions by citing another study that followed 2,907 men for 17 years. Of those men, there were five cases of metastasis, with just two being potentially preventable. He also cites the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam study which followed over 3,000 men with a negative sextant biopsy for 11 years and recorded just seven (.02 percent) deaths during that time. Dr. Vickers concludes that the number of men whose prostate cancer would have to be identified and treated in order to save one life is very large and MRI-targeting is leading to excessive overdiagnosis and overtreatment. Dr. Vickers then states that while there should be a clear clinical indication for MRI, such as negative biopsy with rising PSA, the current National Comprehensive Cancer Network (NCCN) guidelines call for treatment irrespective of the method of detection. Dr. Vickers concludes there is an urgent need for more restrictive use of MRI-targeting, evolved treatment guidelines for MRI-detected tumors, and additional research on oncologic risk of MRI-detected tumors.

Minimally-Invasive BPH Therapies

Posted by Christopher P. Smith, MD, MBA, MSS | Dec 2021

Christopher P. Smith, MD, MBA, MSS, Associate Professor of Urology at Baylor College of Medicine in Houston, Texas, considers data on prostatic urethral lift (PUL) and water vapor therapy for benign prostatic hypertrophy (BPH), and analyzes three case studies using the treatments. He begins with an overview of his case studies of men with BPH who all have an International Prostate Symptom Score (IPSS) above 19 and are on tamsulosin but are struggling with the lack of full relief and side effects of the medication. Dr. Smith then discusses the 2021 AUA guidelines for BPH treatment supporting the use of the IPSS at each patient visit to track symptoms and engage patients in early discussions of surgical options in the case of inadequate medications. He continues by summarizing data on the use and efficacy of PUL and water vapor therapy for BPH: a study on the adoption, safety, and retreatment rates of prostatic urethral lift found an increase in the use of the treatment of 10.4% from 2014 to 2018; PUL has passed GreenLight as a preferred procedure as of 2019, accounting for 30% of all BPH procedures; the L.I.F.T. trial and REZUM II trial found that PUL produced significant improvement in symptom scores, quality of life and flow rate when compared to a control; a prospective, randomized, multinational study of PUL versus transurethral resection (TUR) of the prostate found that PUL patients had a more rapid return to baseline activities than TUR patients by 6 days; the MedLift study showed that PUL patients experienced a 75% improvement in IPSS compared to a 34% improvement in control patients; PUL has also been found to have the lowest complications compared to Rezum, TURP, and GreenLight; a study comparing durability predictors after PUL found that men with worse disease states were found to need retreatment at higher rates; PUL is capable of improving ejaculatory function following treatment, while water vapor therapy reduces it; and there has been no recorded difference in outcomes between groups with or without prior prostate surgery. Dr. Smith concludes by stating that all three of his cases were treated with PUL, leading to their IPSS dropping to below 5 and them being taken off of medication.

Early Detection of Prostate Cancer: Navigating the Challenges in 2021

Posted by E. David Crawford, MD | Dec 2021

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 challenges of early detection of prostate cancer (PCa) and recommends a prostate-specific antigen (PSA) cut-off of 1.5 ng/ml. He begins by briefly summarizing different screening guidelines, noting particularly that the United States Preventive Services Task Force (USPSTF) has raised concerns about PCa early detection, asserting that there is too much overtreatment. Dr. Crawford argues, however, that evidence shows that a reduction in PSA screening resulted in a rise in metastatic prostate cancer across the United States. Because most diagnostic testing is completed by family practice physicians who may not understand the nuances of PSA testing, Dr. Crawford recognizes that they need a simple message from urologists. He states that a PSA of >1.5 ng/ml is a good surrogate for benign prostatic hyperplasia (BPH), PCa, and PCa risk, and explains that patients with a PSA of 1.5 ng/ml to 4.0 ng/ml may be in a “danger zone” and require additional testing. Dr. Crawford contends that patients do not need to make an informed decision about getting a PSA test, and that PSA testing should be considered as routine as measuring a patient’s weight or cholesterol, especially since more than 70% of men will have a PSA of less than 1.5 and will not require further screening for another 5 to 10 years. He then explains that an abnormal PSA alone should not guide biopsy decisions, though, and suggests that using tests like 4Kscore and SelectMDx in conjunction with MRI can reduce unnecessary biopsies. Dr. Crawford concludes by reiterating the importance of simple messaging to move forward with effective screening and early detection of PCa.

Panel Discussion – Focus on PSMA

Posted by Phillip J. Koo, MD | Dec 2021

Phillip J. Koo, MD, Division Chief of Diagnostic Imaging and Northwest Region Oncology Physician Executive at the Banner MD Anderson Cancer Center in Phoenix, Arizona, leads a panel discussion focused on PSMA PET-CT’s expanding role in prostate cancer screening and diagnosis. The conversation begins with a look at how PSMA ligands are produced and distributed and what this means for access. Jérémie Calais, MD, MSc, Director of the Clinical Research Program of the Ahmanson Translational Theranostics Division of the Department of Molecular and Medical Pharmacology at UCLA, explains the differences between Gallium-68 PSMA-11 and 18F-DCFPyL, noting that the capacity of production and distribution is greater for the latter than the former. He argues, however, that the tracer used does not ultimately matter. E. David Crawford, MD, Professor of Urology at UCSD, observes that there have not actually been any comparative trials of gallium vs. PyL scans, and he suggests that there might be subtle differences in efficacy. Dr. Calais agrees that there is some disparity, but he does not think they are significant enough to affect staging or clinical management decisions. The discussion continues with a brief consideration of PSMA’s potential in theranostics and a look at whether PSMA scans can be trusted without confirmation from biopsy. Dr. Crawford notes that while biopsies are important and should be obtained when possible, as trust grows in the PSMA scans they may become less necessary. Dr. Calais and Dr. Koo then consider the potential for PSMA tests to be reimbursed, observing that they are not yet covered by Medicare but that there is a potential that they will be covered by insurance relatively soon. Dr. Crawford then asks whether the older CT and bone scans will be replaced by scans like PSMA, and the panelists conclude that they inevitably will but that costs will make this shift take some time.