Gleason score and the risk of cause-specific and all-cause mortality following radiation with or without 6 months of androgen deprivation therapy for men with unfavorable-risk prostate cancer

Abstract

We evaluated whether a differential impact of adding 6 months of androgen deprivation (ADT) to radiation therapy (RT) on all-cause (ACM), prostate cancer-specific (PCSM), and other-cause mortality (OCM) in men with unfavorable-risk prostate cancer (PC) exists within Gleason score (GS) subgroups. Individual patient data from 743 men with unfavorable-risk PC from two randomized ADT trials were utilized. Competing risks and Cox regression were used to determine whether adding 6 months of ADT to RT significantly impacted PCSM, OCM, and ACM within GS subgroups. Men with GS 9/10 versus ≤8 were significantly more likely to be over 75 (23.3 versus 12.7 %; p = 0.03). At a median follow-up of 11.93 and 11.81 years in the 683 and 60 patients with GS ≤8 and GS 9/10, 315 (46.1 %) and 44 (73.1 %) died, respectively. ADT in men with GS ≤8 was associated with significantly decreased ACM (adjusted hazard ratio (AHR) 0.66; 95 % confidence interval: 0.52–0.82; p < 0.001) and PCSM (0.43; 0.28–0.66; p < 0.001) but no significant difference in OCM (0.90; 0.68–1.17; p = 0.43) Among men with GS 9/10 PC ADT significantly reduced PCSM (0.33; 0.11–0.99; p = 0.048) but not ACM (0.79; 0.38–1.61; p = 0.51) and increased OCM (2.16; 0.81–5.79; p = 0.12), resulting in opposite effects of ADT on OCM by the GS subgroup such that the relative AHR of OCM in GS 9/10 versus ≤8 was nearly significantly increased (2.42 [0.87,6.71]; p = 0.09). While ADT reduced PCSM risk overall, survival was not prolonged in men with GS 9/10 due to ADT-driven increased OCM, which supports the hypothesis that older men with significant comorbidity may not experience prolonged survival when ADT is added to RT.