Identification of comorbidities that place men at highest risk of death from androgen deprivation therapy before brachytherapy for prostate cancer

Purpose: To determine which specific comorbidities predispose men to excess mortality by androgen deprivation therapy (ADT) given before and during brachytherapy for prostate cancer. Methods and Materials: We analyzed 5972 men with T1c-T3b prostate cancer treated with brachytherapy-based radiation with or without neoadjuvant ADT. Cox multivariable analysis with propensity scoring was used to determine if ADT was associated with increased all-cause mortality (ACM) in men divided into groups stratified by cardiac comorbidities. Tests for interaction between risk group and outcome were performed. Results: ADT was associated with increased ACM in men with a history of myocardial infarction or congestive heart failure, regardless of whether they underwent revascularization (adjusted hazard ratio [AHR], 2.1 [95% confidence interval {CI}, 1.02-4.17; p=0.04]) or not (AHR, 1.8 [95% CI, 1.05-3.20; p=0.03]), but this effect was not seen in men with less severe comorbidity. However, among men with diabetes, there was a significant interaction with risk group (p=0.01) such that ADT was associated with excess mortality in men with low-risk disease (AHR=2.21 [1.04-4.68]; p=0.04) but not in men with intermediate or high-risk disease (AHR, 0.64 [0.33-1.22]; p=0.17). Conclusions: ADT was associated with excess ACM in all patients with a history of congestive heart failure or myocardial infarction, regardless of whether they were revascularized, and in diabetics with low-risk disease. ADT for gland downsizing before brachytherapy should be avoided in these men.