Androgen deprivation therapy (ADT) using gonadotropin-releasing hormone (GnRH) agonists decreases prostate cancer mortality (PCM) and, in some instances, all-cause mortality in men with intermediate/high-risk or locally advanced prostate cancer [1], [2]. It is estimated that up to 50% of men with prostate cancer will receive ADT at some point during their treatment [3].

ADT has been associated with increased risks of myocardial infarction (MI) and cardiovascular mortality (CVM) [4], [5], [6], but questions remain concerning the magnitude of risks and their association with ADT duration [7]. Men with pre-existing comorbidities or prior cardiovascular disease (CVD) may be at a higher risk of CVM when treated with GnRH agonists [8], [9], which have been associated with metabolic changes including increases in weight, body fat percentage, cholesterol, triglycerides, and decrease in insulin sensitivity [10].

In 2010, a science advisory consensus statement described a possible “relation between ADT and cardiovascular (CV) events and death” [11]. The U.S. Food and Drug Administration required labeling of GnRH agonists, describing an increased risk of “certain CVDs” [12]. However, numerous randomized trials and a meta-analysis suggested that ADT was not significantly associated with increased CVM [13], [14], [15], [16], [17], [18].

Given ongoing controversy, we harnessed almost 20 yr of follow-up data from the large, randomized clinical trial NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9202 to evaluate the long-term relationship between ADT duration and CVM for men with locally advanced prostate cancer.