Biochemical response to neoadjuvant androgen deprivation therapy before radiation therapy and the risk of death in patients with unfavorable-risk prostate cancer: A secondary analysis of a randomized clinical trial

Introduction: A prostate-specific antigen (PSA) level >0.5 ng/mL after 9 to 10 weeks of neoadjuvant androgen deprivation therapy and before radiation therapy (RT) was associated with an increased PSA-failure risk; however, the impact on all-cause mortality (ACM) risk after adjusting for serum testosterone level remains unknown.

Methods: From 2005 to 2015, 350 patients with localized, unfavorable-risk prostate cancer (PC) were randomly assigned to receive androgen deprivation therapy and RT plus docetaxel vs standard of care (SOC) with androgen deprivation therapy and RT. Multivariable Cox regression analyses were used to assess whether a significant association existed between PSA (continuous and categorized as ≤0.5 vs > 0.5 ng/mL) measured at 9 to 10 weeks after randomization and ACM risk, adjusting for known PC prognostic factors and baseline testosterone level.

Results: After a median follow-up of 10.23 years (interquartile range: 8.07-11.41), 85 patients died (25.30%), 41 from PC (48.24%). PSA level at 9 to 10 weeks after randomization was significantly associated with increased risk of ACM when analyzed as a continuous (adjusted hazard ratio, 1.16; 95% CI, 1.04-1.30; p = .008) or categorical covariate (>0.5 vs ≤ 0.5 ng/mL; adjusted hazard ratio, 1.88; 95% CI, 1.12-3.17; p = .02) after adjusting for covariates.

Conclusions: This study validates that a PSA level >0.5 ng/mL after neoadjuvant androgen deprivation therapy and before RT is prognostic and significantly associated with an increased ACM risk. Patients achieving this endpoint should be considered for enrollment in future randomized trials evaluating the impact of treatment escalation on ACM using a prerandomization stratification by age or validated comorbidity metrics.