ADT Side Effects: Cardiovascular Disease
In a program supported by Verity Pharmaceuticals, E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego; Celestia S. Higano, MD, FACP, Adjunct Professor, Department of Urologic Sciences, University of British Columbia and Medical Director, Prostate Cancer Supportive Care Program, Vancouver Prostate Centre, Vancouver, British Columbia; and Evan R. Goldfischer, MD, MBA, Director, Research Department, Premier Medical Group and President-elect of the Large Urology Group Practice Association (LUGPA), Poughkeepsie, New York, discuss major adverse cardiac events (MACE) as a side effect of androgen-deprivation therapy (ADT).
Dr. Crawford lists the side effects of ADT and shares data comparing risk of diabetes, coronary artery disease (CAD), acute myocardial infarction (MI), sudden cardiac death, and stroke among men with and without ADT. He then displays data that show patients with a history MACE were more likely to experience MACE following ADT, concluding that is consistent with previous publications and studies and pointing to an analysis of data over 10 years from >44,000 prostate cancer patients.
Dr. Higano highlights results of the PRONOUNCE trial. She provides background, highlighting that atherosclerotic cardiovascular disease (ASCVD) is the primary non-cancer cause of death among patients with prostate cancer. Dr. Higano explains the study was terminated due to smaller-than-planned participant numbers and MACE events and no difference being found in the rate of cardiovascular events at 12 months between patients assigned to degarelix or leuprolide. The relative cardiovascular safety of GnRH antagonists compared with agonists remains unresolved. She cites the need for rigorously conducted cardio-oncology trials to better define the cardiovascular risk of new cancer agents, explaining that PRONOUNCE provides a model for interdisciplinary collaboration. Dr. Higano emphasizes the importance of systematic baseline cardiovascular risk assessment and identifying patients at high risk of MACE to ensure they are connected to a cardiologist, rather than selecting one ADT drug over another; she also emphasizes educating patients about risk mitigation through exercise, healthy diet, and not smoking.
Dr. Goldfischer then begins by citing insights from the RADICAL PC study and quoting its conclusions. He points out that ADT can further increase the risk of MACE in patients already at high risk, but ADT may not be the cause of MACE in average, baseline patients; indeed, part of the ADT association with MACE that has been reported may be driven by previously unmeasured cardiovascular risk factors. Dr. Goldfischer emphasizes that for those at high risk of MACE who need ADT, urologists should collaborate with high-risk patients’ primary care physicians, cardiologists, or cardio oncologists to aggressively manage risk.
The panel concludes with a series of follow-up questions from Dr. Crawford as well as take home messages from each of the participants about managing MACE in patients on ADT.
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ABOUT THE AUTHOR
Researcher-physician E. David Crawford, MD, Jack A. Vickers Director of Prostate Research and Professor of Urology at the University of California, San Diego, has devoted his career in medicine to educating the public about men's health issues and finding effective techniques and procedures to address prostate cancer, the most common malignancy affecting men in the United States.
Celestia (Tia) S. Higano, MD, FACP, was formerly a Professor in the Departments of Medicine and Urology, Division of Medical Oncology at the University of Washington, and Clinical Division of Fred Hutchison Cancer Research Center. She is an Adjunct Professor in the Department of Urologic Sciences at the University of British Columbia. She has been the Medical Director of the Prostate Cancer Supportive Care Program at the Vancouver Prostate Centre since 2013.
Dr. Higano received her medical degree from the University of Massachusetts Medical School and completed her residency at the Mayo Graduate School of Medicine in Rochester, MN. She was an oncology fellow under E. Donnall Thomas and Robert B. Livingston at the Fred Hutchison Cancer Research Center and the University of Washington.
Dr. Higano is an internationally renowned expert and clinical researcher focusing on prostate cancer. At UW, she led the prostate cancer clinical research group that participated in developing agents such as zoledronic acid, sipuleucel-T, enzalutamide, apalutamide, abiraterone, radium 223. Over these years, her clinical research has impacted the standards of care for patients with prostate cancer. She is a passionate educator and mentor and has guided many fellows and young faculty at the University of Washington and elsewhere who have chosen an academic career in GU Oncology.
Dr. Goldfischer is a urologist and Director of the Research Department at Premier Medical Group in Poughkeepsie, New York. He received his BA from Tufts University and his MD from Cornell University Medical College. He completed his Internship in General Surgery and his Residency in Urology at the University of Chicago. He then completed a Fellowship in Endourology under the direction of Arthur Smith at Long Island Jewish Medical Center. Dr. Goldfischer received his MBA from the University of Massachusetts and is a Certified Physician Executive. He is the Founder and Chair of the Board of Premier Cares Foundation, which aims to support and educate individuals who are unable to address significant issues like prostate and colon cancer. He has authored more than 100 peer-reviewed abstracts and publications and has lectured on six continents. Dr. Goldfischer has served as the Chair of the Advanced Prostate Cancer Expert Panel for the Public Education Council of the Urology Care Foundation, which is the official foundation of the AUA. He was elected to the LUGPA Board of Directors in 2014 and was elected Secretary of LUGPA in November 2018. Dr. Goldfischer was elected President of LUGPA in 2022 and still serves in that role.
