Perspectives in Urology: Point-Counterpoint Archives

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.

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

Posted by Amirali Salmasi, MD | 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.

Point-Counterpoint: Neoadjuvant Chemotherapy Prior to Cystectomy – Con

Posted by Alan H. Bryce, MD | May 2022

Taking the con side in a point-counterpoint debate, Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, argues that offering neoadjuvant chemotherapy (NAC) to patients with invasive bladder cancer prior to radical cystectomy (RC) may not always be the appropriate decision. He begins by considering what the debate even is, explaining that the NCCN considers NAC followed by radical cystectomy a category 1 recommendation based on high level data. Meanwhile, Dr. Bryce notes, adjuvant chemotherapy is only considered a category 2A recommendation. However, he continues, the NCCN guidelines also mention that patients with “hearing loss or neuropathy, poor performance status, or renal insufficiency may not be eligible for cisplatin based therapy,” and if “cisplatin based therapy cannot be given, neoadjuvant therapy is not recommended.” Dr. Bryce also argues that while clinical trial data strongly favors NAC, real-world patient populations are different from trial populations. He cites a study based on real-world data which found that the patients in the SWOG trial of NAC were younger and fitter compared with national numbers, and which found the survival benefit with NAC to be slight in retrospective data. Additionally, Dr. Bryce observes that about 33 to 41% of patients are ineligible for cisplatin due to their baseline renal function status. He notes that those patients might benefit from adjuvant chemotherapy, but acknowledges there have been few randomized controlled trials in this setting. Dr. Bryce then highlights toxicity issues related to NAC, including increased creatinine, decreased neutrophil, peripheral sensory neuropathy, and tinnitus. He concludes that because real-world patients are older and have more comorbidities than trial populations, NAC perhaps should not be used as widely as guidelines indicate.

PSMA Targeted Therapies and the Role of the Urologist

Posted by Phillip J. Koo, MD | May 2022

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, discusses PSMA targeted therapies for prostate cancer and the urologist’s role in using radiotherapy. He begins by looking at the results of the VISION trial of lutetium-177 PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC), explaining that radioligand therapy significantly increased overall survival and radiographic progression-free survival. Dr. Koo then considers the TheraP trial of lutetium-177 PSMA-617 versus cabazitaxel which saw far better PSA response in PSMA arm than in the cabazitaxel one. He notes that the amount of imaging used in patient selection for TheraP would be impractical in a real-world setting. Dr. Koo also looks at the slate of upcoming clinical trials of PSMA, highlighting the number of combination therapy trials in the CRPC setting, as well as the number of trials looking at PSMA’s potential role in earlier phases of the disease. Finally, Dr. Koo discusses the role of the urologist in the new PSMA era, arguing that urologists need to understand and be comfortable with PSMA since it is an increasingly important tool for treating advanced prostate cancer. He recommends that urologists create advanced prostate cancer clinics featuring targeted radiotherapy clinics.