International Prostate Cancer Update Archives

Updates in ADT: Managing Adverse Effects

Posted by Laurence Klotz, MD, FRCSC | 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.

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 Daniel P. Petrylak, MD | 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.

Presentations from the 1st Annual Advances in Men’s Health

Posted by David Utz | Oct 2021

These lectures were presented during the 1st Annual Advances in Men’s Health conference in August 22-25, in Whitefish, Montana.

Focal Cryosurgery: Outcomes and Observations

Posted by Thomas J. Polascik, MD, FACS | 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.

Updates on PSMA Imaging and PSMA CAR T Therapy

Posted by Daniel P. Petrylak, MD | 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, discusses CAR T therapy for prostate cancer and the ways in which its efficacy is impacted by tumor type and stem memory T cells (TSCM). He begins by reviewing the VISION Trial of LuPSMA which found a 40% reduction in the risk of death and 4-month improvement in median overall survival (OS) versus standard of care (SOC) alone. He also looks at the FDA approval of PYLARIFY in May 2021, the first commercially available PSMA PET imaging agent for prostate cancer. Dr. Petrylak then poses the question of how to combine immunotherapy with PSMA. He suggests that the answer may exist in CAR T therapy despite its historically poor results in solid tumors, and discusses the different types of CAR T cells along a spectrum of less differentiated, self-renewing, and long-lived cells to more differentiated, less stem-like cells. Dr. Petrylak states that TSCM, which exist on the less differentiated side of the spectrum, are key to CAR T therapy’s success in solid tumors based on evidence from a study using a TSCM-based approach that found 100% tumor elimination in animals at standard and low doses after 2 weeks. He reviews early information on a Phase I trial of TSCM based CAR T therapy on mCRPC patients which appears to have positive early results. Dr. Petrylak concludes that PSMA is proving to be an excellent target for imaging and therapy in mCRPC and CAR T therapy may be able to enhance treatment as well.