Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08

Background: Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease. Objective: We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial. Design, setting, and participants: A total of 1979 men with clinically localized (T1b–2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors. Outcome measurements and statistical analysis: The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed diseasespecific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA. Results and limitations: Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard