Neoadjuvant hormonal therapy use and the risk of death in men with prostate cancer treated with brachytherapy who have no or at least a single risk factor for coronary artery disease

Background: Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown.

Objective: To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD.

Design, setting, and participants: This retrospective study cohort consisted of 5411 men with low-risk PCa (prostate-specific antigen [PSA] <10 ng/ml, Gleason score 6, and clinical stage T1-T2a); 4365 men with intermediate-risk PCa (PSA 10-20 ng/ml or Gleason score <8 or clinical stage <T3); and 1360 men with localized or locally advanced, high-risk PCa consecutively treated in a community-based, multi-institutional setting between 1991 and 2006. CAD risk factors included at least a history of diabetes mellitus, hypercholesterolemia, or hypertension. The median follow-up for men with low-, intermediate-, and high-risk PCa were 4.1, 4.4, and 4.6 yr, respectively.

Interventions: Men were treated with or without a median duration of 4 mo of NHT followed by brachytherapy with or without supplemental external-beam radiation therapy (EBRT).

Outcome measurements and statistical analysis: Cox regression multivariable analyses were performed to assess whether NHT use affected the risk of ACM in men with low-, intermediate-, and high-risk PCa, adjusting for age; year of brachytherapy; supplemental EBRT use; the presence of CAD risk factors; treatment propensity score; and known PCa prognostic factors, including pretreatment PSA level, biopsy Gleason score, and clinical stage.

Results and limitations: NHT use was associated with a significantly increased risk of ACM in men with low-risk PCa (adjusted hazard ratio [HR]: 1.27; 95% confidence interval [CI], 1.07-1.51; p<0.01) but not in men with intermediate-risk (adjusted HR: 1.13; 95% CI, 0.96-1.35; p=0.15) or high-risk PCa (adjusted HR: 0.86; 95% CI, 0.66-1.13; p=0.28). Using an interaction model for the low-risk group, NHT use was associated with a significantly increased risk of ACM in the subgroup of men with at least a single CAD risk factor (adjusted HR: 1.36; 95% CI, 1.07-1.74; p=0.01) but not for men with no CAD risk factors (adjusted HR: 1.19; 95% CI, 0.95-1.51; p=0.13).

Conclusions: For men with no or at least a single risk factor for CAD, NHT use is associated with an increased risk of ACM in the setting of low-risk but not intermediate- or high-risk PCa. This effect is driven by the subgroup of men with at least a single risk factor for CAD. These results warrant prospective validation given the widespread use of NHT for prostate downsizing prior to brachytherapy.