Androgen Deprivation Therapy Use in the Setting of High-Dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

Abstract

The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is standard of care for men with intermediate and high-risk prostate cancer (PC). However, whether competing mortality impacts the ability of ADT to improve survival remains unanswered. We calculated a competing mortality (CM) risk score using a Fine-Gray semi-parametric model including age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for non-metastatic PC. Fine and Gray competing risk regression was used to assess whether ADT reduced the risk of prostate cancer-specific mortality (PCSM) for men with low vs. high risk of CM amongst the 4,550 patients within the intermediate and high-risk cohort adjusted for established PC prognostic factors, year of treatment, site, and ADT treatment propensity score. After a median follow-up of 8.4 years 1,065 men died; 89 (8.36%) from PC. Among men with a low CM score, ADT use was associated with a significant reduction in the risk of PCSM (adjusted HR (AHR) = 0.35, 95% CI = 0.14 to 0.87, P = 0.02) but not in men with a high CM score (AHR = 1.33, 95% CI = 0.77 to 2.30, P = 0.30). Given the differing direction of the AHR for ADT use amongst men with high vs low CM score the interaction term was significant (P = 0.01). Adding ADT to high-dose RT appears to be associated with decreased PCSM in men with low but not high CM. These data should serve to heighten awareness about the importance of considering competing risks when determining whether or not to add ADT to RT to treat men with intermediate or high-risk PC.