The prognostic impact of prostate-specific antigen at 6 months after post-prostatectomy radiotherapy: An individual patient data analysis of two NRG oncology randomized trials.

254 Background: We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) within 6 months of completion of salvage radiotherapy (RT) in patients treated with RT with or without hormone therapy (HT). Methods: Individual patient data were obtained from 2 randomized trials (NRG’s RTOG 0534 and RTOG 9601) evaluating salvage RT with or without HT. HT was either androgen deprivation therapy (ADT) for 4-6 months or bicalutamide for 2 years. The lowest PSA recorded within 6 months after RT completion was identified and categorized as ≤ or >0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox proportional hazards regression was used to estimate hazard ratio (HR) with 95% confidence intervals to characterize the association of PSA within 6 months post-RT completion with OS and MFS while adjusting for age, Gleason score, trial, and HT use. Five-year MFS and 10-year OS rates were estimated using the Kaplan-Meier method. Results: Among a total of 2,373 patients, 1833 (77%) patients achieved a nadir PSA ≤0.1 and 540 (23%) did not. Among patients who did not get HT, 50% did not reach the milestone compared to only 6% of patients who got HT. PSA ≤0.1 ng/mL was associated with better OS (HR 0.27 [95% CI 0.12-0.6], p=0.001) and better MFS (HR 0.25 [95% CI 0.13-0.47], p<0.0001). The interaction test showed that the improved OS/MFS in patients who achieved the nadir was more prominent in those who did not receive HT compared to those who received HT. Five-year MFS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 94% vs 81%, 92% vs 87%, and 91% vs 93%, respectively, based on PSA ≤ vs >0.1. Ten-year OS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 87% vs 76%, 84% vs 84%, and 82% vs 83%, respectively, based on PSA ≤ vs >0.1. Conclusions: PSA >0.1 ng/mL within 6 months was prognostic for OS and MFS in patients treated with salvage RT in the post-prostatectomy setting. This finding allows better patient counseling and can guide clinical trial design for treatment intensification or de-intensification in patients receiving salvage RT.