Defining the optimal approach to the patient with postradiation prostate-specific antigen recurrence using outcome...

Optimal management remains unknown following prostate-specific antigen (PSA) failure when considering comorbidity and PSA kinetics at recurrence. In order to define randomized controlled trials (RCTs) that can address this issue, this study examined factors associated with the risk of death following PSA failure.

Of 206 men randomized to RT with or without 6 months of androgen suppression therapy (AST), 108 sustained PSA failure and began AST when PSA approached 10 ng/mL and formed the study cohort. Cox regression multivariable analysis was used to determine factors associated with death following PSA failure.

After a median follow-up of 10.3 years of 108 men with PSA failure, 64 (59%) died, with 22 (34%) dying of prostate cancer (PC). Increasing PSA velocity at recurrence was associated with a significant increase in the risk of death (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.45; P = .03). Among men with no/minimal versus moderate/severe comorbidity, PC comprised 42% (20 of 48) versus 12.5% (2 of 16) of all deaths, respectively. Estimates of PC-specific and all-cause death were significantly higher when PSA velocity was greater than as compared with the median or less in men with no/minimal (P < .008) but not moderate/severe comorbidity (P > .15).

Despite unfavorable PSA kinetics at recurrence, unhealthy men may not benefit from AST; RCTs examining intermittent AST versus surveillance are needed. For healthy men with unfavorable PSA kinetics at recurrence, PC death rates are high despite AST, which warrants RCTs to evaluate the impact on death when adding agents that prolong survival in men with metastatic castration-resistant PC to AST.