Long-Term Results of NRG/RTOG 9601, a Randomized Trial of Radiation With or Without Antiandrogens in Patients Receiving Salvage Prostate Bed Radiation Therapy Postprostatectomy.

[PURPOSE] Salvage radiation therapy (RT) is used in men with prostate cancer (PC) recurrence following radical prostatectomy signaled by a persistent or delayed elevation in prostate specific antigen. It was previously reported that the use of antiandrogen therapy (AAT) with RT improved cancer control and overall survival (OS). Long-term follow-up results are presented in this study.

[METHODS AND MATERIALS] From 1998 to 2003, 760 eligible postradical prostatectomy patients with stage pT3N0 or with pT2N0 and positive margins and prostate specific antigen from 0.2 to 4.0 ng/mL were randomly assigned on a double-blinded, placebo-controlled trial of RT + placebo versus RT + AAT (24 months of bicalutamide, 150 mg daily) during and after RT (64.8 Gy in 36 fractions prostate bed). The primary endpoint was OS estimated using Kaplan-Meier method. Time to PC death and metastatic PC (competing risk of death without an event) was estimated using cumulative incidence. The hazard ratio (HR) was obtained using Cox models (OS) and subdistribution HRs (sHRs) used the Fine-Gray model (time to PC death and metastatic PC).

[RESULTS] Median follow-up for surviving patients was 18.9 years. OS at 18 years was 53% (95% CI, 47%-58%) for RT + AAT and 43% (95% CI, 38%-49%) for RT + placebo (adjusted HR = 0.82; 95% CI, 0.67-1.00; 1-sided P = .025). The 18-year incidence of centrally reviewed PC deaths was 18% (95% CI, 14%-22%) RT + AAT and 28% (95% CI, 23-33%) RT + placebo (unadjusted sHR = 0.63; 95% CI, 0.46-0.84; 2-sided P = .002). The 18-year incidence of metastatic PC was 22% (95% CI, 18-26%) and 31% (95% CI, 26-36%) for AAT and placebo arms, respectively (unadjusted sHR = 0.62; 95% CI, 0.46-0.83; 2-sided P = .001).

[CONCLUSIONS] Long-term results of 24-month duration AAT during and after salvage RT are consistent with the primary report with significantly improved long-term OS, reduced incidence of metastatic PC, and PC death for RT + AAT. In comparison with previous reports, the improvement in OS with AAT has risen from 5% at 12 years to 9.8% at 18 years.