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Updates in Treatment Using ADT and Anti-Androgens

Updates in Treatment Using ADT and Anti-Androgens

Posted by | 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.

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High Intensity Focused Ultrasound for Prostate Cancer

Posted by | 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.

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Practice Evaluation

Posted by | May 2022

Grand Rounds in Urology Contributing Editor Neil H. Baum, MD, Professor of Urology at Tulane Medical School, goes over four steps to conduct a medical practice evaluation in order to help improve a practice’s efficiency or prepare it for sale or merger. He begins by observing that the road to success in healthcare has become increasingly complicated as regulation and costs have increased, and technology has developed. Dr. Baum then introduces the first step in performing a practice evaluation: identifying long-term goals and motivation behind the practice. He explains that the doctor/owner must ask themselves where they are in their career and consider whether they plan to sell or merge in the near future. The answers to these questions may lead to further questions about how sustainable the practice is without the full time involvement of the doctor, or about how the doctor/owner can make the practice more attractive to potential buyers. Dr. Baum then moves on to the second step: evaluate practice essentials. These essentials include profit/loss statements, patient volume, status of competitors, patient satisfaction, the status of accounts receivable, and more. Dr. Baum follows this with the third step: measurement of provider productivity. He explains that practice owners should determine how productive doctors in their practice are by looking at the number of patients seen per provider during each half-day session. He suggests that once they have gathered this data, practice owners can determine how to make the lower producers more productive. Finally, Dr. Baum goes over the fourth step: evaluate team talent and morale. He observes that staff salaries represent a practice’s largest expense, and he notes that staff are largely responsible for patient satisfaction. Dr. Baum recommends having an employee review every quarter while also holding regular staff meetings and conducting employee engagement surveys.

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Role of Prostate Brachytherapy in Gleason 8-10 Disease

Posted by | May 2022

As part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Peter F. Orio III, DO, MS, Vice Chair of Network Operations for Dana-Farber/Brigham and Women’s Cancer Center Department of Radiation Oncology and Associate Professor of Radiation Oncology at Harvard Medical School in Boston, Massachusetts, discusses brachytherapy’s role in treating high-risk prostate cancer (PCa). He shares the largest prostatectomy series to report cause-specific survival (CSS) by biopsy Gleason score (and the largest prostatectomy series to report CSS in the prostate-specific antigen [PSA] era), highlighting data that demonstrate that men with T3 disease have a 38 percent chance of prostate-cancer-specific mortality (PCSM) and men with a Gleason score of 8-10 have a 34 percent chance of PCSM. Further, long-term surgical biochemical progression-free survival (bPFS) among men with a Gleason score of 8-10 is on the order of 30-40 percent. Dr. Orio then displays data from a comparative analysis of PSA-free survival outcomes for patients with high-risk PCa by radical therapy. It shows that external-beam radiation therapy (EBRT) with brachytherapy (with or without androgen-deprivation therapy [ADT]) has better PSA-free progression than do other radical therapies. He cites data that show when brachytherapy is added to EBRT, patient outcomes improve. He then introduces three clinical trials examining EBRT with and without brachytherapy to examine more closely. In the first trial, at a median follow-up of 8.2 years, patients treated with EBRT with a brachytherapy component had half the biochemical failure compared with patients treated with EBRT alone. Similarly, another randomized trial of EBRT alone or combined with high-dose brachytherapy boost showed similar improved outcomes, with better biochemical relapse-free survival at five, seven, and 10 years for patients who underwent the combined therapy. Dr. Orio then turns to the ASCENDE-RT Trial, which compared a low-dose-rate prostate brachytherapy (LDR-PB) to a dose-escalated EBRT (DE-EBRT) for patients with high- and intermediate-risk PCa. Data showed a benefit to the LDR-PB, with an absolute difference in the proportion of patients free of recurrence of nearly 21 percent at nine years. Similar results occurred among intermediate-risk patients and high-risk patients. Dr. Orio goes on to compare the progression-free survival at seven years among high risk patients who received the LDR-PB (83 percent) with the surgical bPFS of 30-40 percent, concluding that brachytherapy can spare many men the need for salvage therapies. He then addresses toxicity concerns about the LDR-PB, explaining that practitioners should avoid the dragging of seeds to the membranous urethra, where they have the potential to cause a urethral stricture. Dr. Orio explains that doctors can decrease toxicity by identifying the apex of the prostate, making it easier to control placement of the seeds and avoid toxicity. He goes on to explain other solutions to reduce toxicity such as using a gel spacer between the prostate and the rectum. Dr. Orio cites one additional study confirming that EBRT with brachytherapy leads to better patient outcomes compared with radical prostatectomy or EBRT alone. Dr. Orio advises that patients with intermediate- or high-risk PCa receiving EBRT +/- ADT should be offered brachytherapy as a dose escalation strategy because it is proven with Level 1 evidence. He explains that the American Society of Clinical Oncology (ASCO) stated that eligible intermediate- and high-risk PCa patients choosing EBRT with or without ADT should be offered brachytherapy. Dr. Orio states that a rising PSA condemns many men to expensive, toxic, and quality-of-life-reducing treatments and asks if society is prepared for this cost to normalize overall survival. He asserts that we should instead consider using brachytherapy in those with higher-risk disease.

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Point-Counterpoint: Neoadjuvant Chemotherapy Prior to Cystectomy (Pro)

Posted by | May 2022

Taking the pro side in a point-counterpoint debate, Amirali Salmasi, MD, Assistant Professor of Urology at the University of California, San Diego, argues that neoadjuvant chemotherapy (NAC) should be offered to any “fit” patient with invasive bladder cancer before radical cystectomy (RC). After noting that survival outcomes for invasive bladder cancer after cystectomy are not great in general, Dr. Salmasi considers decades of trial data on the addition of NAC to RC. He looks at the SWOG-8710 trial, two Nordic trials, the BA06 30894 trial, a trial of ddMVAC, and more, all of which indicate that NAC improves outcomes significantly. Dr. Salmasi also notes that these trials did find that NAC increased perioperative risks. He then considers the potential role of adjuvant chemotherapy, observing that the limited data available suggest that NAC is superior to adjuvant treatment. Dr. Salmasi concludes with a brief discussion of how urologists and oncologists should optimize the use of NAC by researching therapy combinations, duration, patient selection, and biomarkers.

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