Prostate Cancer: Androgen Deprivation Therapy May Be Harmful For Some Men

David R. Ziehr B.S., MD Candidate Harvard Medical Interview with:
David R. Ziehr B.S., MD Candidate
Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Response: Androgen deprivation therapy (ADT), commonly achieved with gonadotropin-releasing hormone agonists or antagonists, is a mainstay of prostate cancer therapy. While randomized controlled trials demonstrate that ADT improves survival among men with unfavorable risk prostate cancer, retrospective studies have suggested that some men with comorbid illnesses such as heart disease may not derive a benefit from—or may even be harmed by—ADT. However, the nature of this harm has not been characterized. We studied over 5000 men with prostate cancer who were treated with brachytherapy (implanted radioactive seeds) with or without ADT. We analyzed the men based on pre-treatment cardiac comorbidity and examined the association between ADT and death from cardiac causes. We found that among men with congestive heart failure or a past myocardial infarction (MI), Androgen deprivation therapy was associated with a three-times greater risk of death from heart disease. However, Androgen deprivation therapy was not associated with greater risk of cardiac mortality in men without heart disease or with a risk factor for heart disease, such as diabetes, hypertension or hyperlipidemia.

Medical Research: What should clinicians and patients take away from your report?

Response: Our findings suggest that men with congestive heart failure or a past MI may be harmed by Androgen deprivation therapy. Among these men, ADT was associated with a five percent absolute excess risk of cardiac mortality in five years. However, we did not observe an association between Androgen deprivation therapy and cardiac mortality among men with less severe heart disease. When prescribing Androgen deprivation therapy for prostate cancer, physicians should bear in mind both their patients’ prostate cancer and heart health. There may be some scenarios in which ADT should be avoided altogether, such as for gland downsizing prior to brachytherapy for a man with low-risk prostate cancer and coexisting coronary artery disease. Men with prostate cancer should ally with their doctors to ensure that they are taking steps to prevent or treat heart disease and its risk factors, such as diabetes, hypertension or hyperlipidemia, and smoking.

Medical Research: What recommendations do you have for future research as a result of this study?

Response:  Despite mounting evidence that Androgen deprivation therapy may cause harm among some men with prostate cancer—and that such harm may be obviated with diet, exercise, and perhaps agents like metformin—the mechanism by which Androgen deprivation therapy exacerbates heart disease is not well characterized. Along with mechanistic studies, work on strategies for the prevention of Androgen deprivation therapy-associated harm is needed. Further, it is unclear if novel androgen depleting agents such as abiraterone and enzalutamide are similarly capable of placing men with heart disease at risk of premature cardiac death.


Association of androgen deprivation therapy with excess cardiac-specific mortality in men with prostate cancer

David R. Ziehr, Ming-Hui Chen, Danjie Zhang, Michelle H. Braccioforte, Brian J. Moran, Brandon A. Mahal, Andrew S. Hyatt, Shehzad S. Basaria, Clair J. Beard, Joshua A. Beckman, Toni K. Choueiri, Anthony V. D’Amico, Karen E. Hoffman, Jim C. Hu, Neil E. Martin, Christopher J. Sweeney, Quoc-Dien Trinh, Paul L. Nguyen. Association of androgen-deprivation therapy with excess cardiac-specific mortality in men with prostate cancer. BJU International, 2014; DOI: 10.1111/bju.12905