The Dose-Dependent Effect Of ADT For Localized Prostate Cancer On Adverse Cardiac Events

The Dose-Dependent Effect Of Androgen Deprivation Therapy For Localized Prostate Cancer On Adverse Cardiac Events - Highlights of a recent publication 

Article Title:  THE DOSE-DEPENDENT EFFECT OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER ON ADVERSE CARDIAC EVENTS

ABSTRACT

Objectives: To investigate the dose-dependent effect of androgen deprivation therapy (ADT) on adverse cardiac events in elderly men with non-metastatic prostate cancer (PCa) stratified according to life expectancy (LE).

Patients and methods: 50,384 men diagnosed with localized PCa between 1992 and 2007 were identified within the SEER registry areas. We compared those who did receive ADT vs. those who did not within 2 years of PCa diagnosis, calculated as monthly equivalent doses of Gonadotropin-releasing hormone (GnRH) agonists (<8, ≥8 doses), or orchiectomy. Men were further stratified according to LE (<5, 5-10, >10 years). Adjusted Cox hazard models assessed the risk of new-onset coronary heart disease (CHD), acute myocardial infarction (AMI), sudden cardiac death (SCD), cardiac–related interventions, as well as any of these events.

Results: Overall, patients receiving GnRH agonists were more likely to experience a cardiac event, with the most pronounced effect among those receiving ≥8 doses (Hazard ratio [HR] (<8 doses): 1.13, 95% CI: 1.09-1.16, and HR (≥8 doses): 1.18, 95% CI: 1.14-1.22, both p<0.001). The effect of prolonged (≥8 doses) GnRH agonist use on cardiac events was sustained across all strata of LE; however, it was not among men with a LE of <5 years and when use of GnRH agonists was limited to <8 doses (Hazard ratio [HR]: 0.99, 95% CI: 0.67- 1.46, p=0.964). The use of GnRH agonists was associated with a higher risk of CHD (HR (<8 doses): 1.13, 95% CI: 1.09-1.17 and HR (≥8 doses): 1.17, 95% CI: 1.13-1.21, both p<0.001). Conversely, the use of GnRH was generally not associated with an increased risk of AMI or SCD, except for men who received ≥8 doses of GnRH agonists and LE of ≥5 years, who were at a significantly higher risk of SCD (HR (LE 5-10y): 1.19, 95% CI: 1.06- 1.33, p=0.003 and HR (LE >10y): 1.16, 95% CI 1.04-1.29, p=0.006). Finally, orchiectomy was not associated with overall cardiac events, AMI, SCD, and was protective with regard to cardiac-related interventions (HR: 0.78, 95% CI 0.68-0.90, p=0.001).

Conclusion: Exposure to ADT with GnRH agonists is associated with increased risk of cardiac events in elderly men with localized PCa and a decent LE. Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged LE. Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.

Authors: Marianne Schmid M.D.1,2, Jesse D. Sammon D.O.3 , Gally Reznor1, Victor Kapoor M.D.3, Jacqueline M. Speed M.D.1, Firas A. Abdollah M.D.3, Akshay Sood M.D.3, Felix K.-H. Chun M.D.2, Adam S. Kibel M.D.1, Mani Menon M.D.3, Margit Fisch M.D.2, Maxine Sun B.Sc.1 and Quoc-Dien Trinh M.D.1

1Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA 

2Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

3Vattikuti Urology Institute Center for Outcomes Research Analytics and Evaluation, Henry Ford Health System, Detroit, Michigan, USA

Presented by: Thomas E. Keane, MBBCh, FRCSI, FACS

Professor and Chairman of the Department of UrologyMedical University of South Carolina, Charleston, SC USA

Thomas E. Keane, MBBCh, FRCSI, FACS specializes in managing prostate, bladder, and renal cancers. An avid researcher, Dr. Keane has served as principal investigator or coinvestigator on more than 20 major clinical and preclinical studies, funded by grants from the National Institutes of Health as well as industry-funded. Much of his work focuses on innovative concepts in translational research, including utilizing human tumor xenografts to investigate the efficacy of new therapies as they relate to GU malignancies with particular reference to cytotoxic agents, sphingolipids, and boron-containing compounds. He holds a U.S. patent for BNCT in prostate cancer and sphingolipid derivatives and their use.

 

Dr. Keane’s research has led to publication of more than 100 articles peer-reviewed in such journals as Cancer Research, The Journal of Urology, Urologic Oncology, and the Journal of Clinical Investigation. He provides editorial services to publications ranging from Urology to the International Journal of Cancer and is coeditor of the text Glenn’s Urologic Surgery, 6th, 7th, and 8th Edition. He is an accomplished speaker, having del