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Updates in ADT: Managing Adverse Effects

Updates in ADT: Managing Adverse Effects

Posted by | Oct 2021

Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research at Sunnybrook Health Sciences Centre, reviews simple interventions physicians can use to improve quality of life and survival as well as to ameliorate unwanted side effects in prostate cancer patients undergoing androgen deprivation therapy (ADT). He explains that there are many commonly known and relatively manageable adverse effects to ADT, but that many family practitioners may not be aware of or interested in dealing with them. The responsibility therefore falls to urologists. Dr. Klotz then discusses the available and developing interventions, as well as the mechanisms of action that underlie them. First, he looks at how statins reduce the adverse effects of metabolic syndrome related to ADT by inhibiting cellular uptake of androstenediol and therefore reducing the substrate available for testosterone synthesis in the castrate environment. Dr. Klotz then considers the benefits of bisphosphonates and monoclonal antibodies like denosumab in helping with osteoporosis, another common side effect of ADT. He also looks at metformin, an inexpensive drug that appears to reduce weight gain in men on ADT, and notes that exercise is an effective way to delay progression of prostate cancer. Dr. Klotz then presents evidence supporting the use of GnRH antagonists to reduce cardiovascular events in men on ADT and discusses new research regarding the role of FSH in obesity.

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Efficacy of Enzalutamide Plus ADT in Men with De Novo (M1) mHSPC Versus Progression to mHSPC: Post Hoc Analysis of the Phase III ARCHES Trial

Posted by | Oct 2021

Daniel P. Petrylak, MD, Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center in New Haven, Connecticut, presents data analysis from the phase III ARCHES trial showing the efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC). He asserts that urologists should be using next generation anti-androgens more often, citing the fact that only about half of patients are being offered such therapies at the time of mHSPC diagnosis. Dr. Petrylak outlines three reasons for this, including lack of access (driven by high cost and staffing availability), lack of understanding of the data, and lack of education. He then summarizes the ARCHES trial specifications, patient characteristics, and the primary endpoint radiographic progression-free survival (rPFS) data, which demonstrate favored outcomes with ENZA combined with ADT, while specifying that mature overall survival (OS) data is not yet available. Dr. Petrylak then discusses secondary endpoint data, which demonstrate that time to prostate-specific antigen (PSA) progression was significantly better in patients who received ENZA and ADT; similarly, ENZA and ADT reduced the risk of starting a new antineoplastic therapy by 72 percent compared with a placebo and ADT. Data also showed patient benefit in terms of time to first symptomatic skeletal event (SSE) as well as time to castration resistance. Dr. Petrylak addresses the question of disease volume in determining which patients ought to receive these next-generation treatments. He examines rPFS across patient subgroups, from patients with just one metastasis all the way up to those with over six metastases, and asserts that all patients across these groups benefited from the ENZA and ADT therapy, dispelling myths that low-volume patients should not be receiving next-generation treatments. Dr. Petrylak concludes that, for patients with castration-sensitive prostate cancer (CSPC), ENZA used with ADT improves rPFS over ADT alone and that the effect is consistent over all volumes of disease, again stipulating that the OS data is maturing, with additional data expected later this year.

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Renal Mass and Localized Renal Cancer: Active Surveillance and Follow-up After Intervention

Posted by | Oct 2021

In part 2 of a 2-part series, Steven C. Campbell, MD, PhD, Professor of Surgery, Associate Director of Graduate Medical Education, Program Director and Vice Chair of Urology, and Eric A. Klein Chair for Urologic Oncology and Education at the Cleveland Clinic’s Glickman Urological and Kidney Institute, presents significant 2021 updates to the American Urological Association (AUA) guidelines on localized renal cancer, focusing on active surveillance (AS) and follow-up. Dr. Campbell, who served as Chair of the AUA Guidelines Panel for Management of Localized Kidney Cancer, begins by looking at the major revisions made to the AS guidelines, particularly with regard to specifications on which patients really should be considered for AS, the intensity of surveillance in different settings, and the role of renal mass biopsy. He then considers the revised guidance around follow-up after intervention. Dr. Campbell explains the general principles behind follow-up, highlighting the need to discuss implications of stage, grade, and histology including risks of recurrence and possible sequelae of treatment, as well as the importance of performing periodic imaging, lab studies, and medical histories in patients with treated malignant renal masses. He also covers what to do if surveillance suggests metastases or local recurrence. Dr. Campbell concludes by discussing risk-based protocols and follow-up guidelines based on risk categories and prior treatment.

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COVID-19 Updates with Congressman Greg Murphy, MD

Posted by | Oct 2021

Congressman Gregory F. Murphy, MD, a practicing urologist and the Representative from North Carolina’s 3rd District, considers how the COVID-19 pandemic is affecting medical institutions, particularly focusing on vaccine mandates. After an introduction from E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, Rep. Murphy notes that COVID fatigue has now transformed into COVID exasperation. He recommends, as most physicians do, that everyone eligible gets vaccinated, observing that the vast majority of people in the ICU with COVID-19 are unvaccinated. Rep. Murphy suggests that vaccine mandates are a more complicated issue, explaining that now that deadlines have passed for staff to get vaccinated at hospitals, many institutions are having to let nurses and other integral staff go due to their beliefs. He also poses the questions of whether or not vaccination will be required on an annual basis and of whether acquired immunity from having had COVID-19 could be considered equivalent to vaccination. Rep. Murphy then briefly considers possible new treatments for COVID-19, noting that although there are several pre-existing drugs on the market that have shown promise for COVID, there is not a profit incentive for these to be tested in COVID trials. The conversation concludes with a brief discussion of current government funding issues related to the debt ceiling, the infrastructure bill, and the reconciliation package.

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Focal Cryosurgery: Outcomes and Observations

Posted by | Oct 2021

Thomas J. Polascik, MD, FACS, Professor of Surgery at Duke University and Director of Surgical Technology at the Duke Prostate and Urological Cancer Center, discusses focal cryosurgery for prostate cancer and its functional outcomes. He introduces, as a typical example of his patients, the case of a 64-year-old mostly healthy man who is concerned with the side effects of radical prostatectomy. Dr. Polascik describes the 21st century prostate cancer patient and discusses how and why doctors’ recommendations are becoming less influential, especially when it comes to active surveillance. He returns to the case of the 64-year-old man and shows how cryo-probes are used in an overlapping manner to create a kill zone, and then outlines the procedure. Dr. Polascik reviews a study on Vitamin D3 as a sensitizer to cryoablation that found that on post-treatment day 9, freezing with Vitamin D3 has near a 98% reduction in cell repopulation compared to just freezing. He discusses functional outcomes such as high rates of continence, failure-free survival rates of about 75% at 5 years, 100% metastasis-free survival, and no infield recurrence of Gleason grade 2 or higher in anterior gland focal cryoablation. Dr. Polascik concludes with a look at the future of focal cryoablation, highlighting its ability to maintain quality of life, serve as durable cancer control, be pain-free, and support rapid recovery.

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