MP72-01\u2003IMPROVEMENTS IN FREEDOM FROM PROGRESSION WITH SHORT TERM ANDROGEN DEPRIVATION THERAPY AND PELVIC LYMPH NODE TREATMENT ADDED TO PROSTATE BED SALVAGE RADIOTHERAPY: THE NRG ONCOLOGY/RTOG 0534 SPPORT TRIAL

Abstract

INTRODUCTION AND OBJECTIVES: Salvage prostate bed radiotherapy (PBRT) results in about 70% 5 yr freedom from progression (FFP). A three arm randomized trial was designed to determine whether there are incremental gains in FFP by adding (i) 4-6 mo of short term androgen deprivation therapy (STAD) to PBRT and (ii) the combination of STAD and pelvic lymph node treatment (PLNRT) to PBRT. METHODS: Patients were randomized to PBRT alone (Arm 1), PBRT + STAD (Arm 2), and PLNRT + PBRT + STAD (Arm 3). The FFP primary endpoint included PSA nadir+2, clinical failure, or death from any cause. The sample size provided 90% power to detect a 10% absolute FFP improvement at 5 yr in Arm 2 compared to Arm 1 and another 10% improvement in Arm 3 compared to Arm 2 (overall alpha of 0.025). Based on 1191 eligible patents with 5 yr minimum follow-up on the third planned interim analysis for efficacy and futility, stepwise comparisons were made to determine if the Haybittle-Peto (HP) threshold boundary of p < 0.001 (one sided) was crossed. Futility evaluation tested the alternative hypotheses at p < 0.001. Adverse events were graded using CTCAEv3.0. RESULTS: From 2008-2015, 1792 patients were enrolled. Of these, 1736 were eligible with a median age of 64 yr, black in 13%, baseline Zubrod status of 0 in 93%, seminal vesicle involvement in 15%, pre-radiotherapy PSA of ⩽1.0 ng/ml in 89%, Gleason score <8 in 83%, and pT2 margin positive or pT3 in 72%. Median follow-up for those living is 5.4 yr. For the 1191 patients in the interim analysis cohort, the 5 yr FFP rates for Arms 1, 2, and 3 were 71%, 83% and 89%. When compared to Arm 1, Arm 3 exceeded the HP boundary with a hazard ratio (HR) 0.44 (95% CI: 0.32-0.59). Arm 3 was then compared to Arm 2, yielding a difference of 6% (p = 0.0063) and an HR of 0.71 (95% CI: 0.51-0.98). In all eligible patients followed for up to 8 years, there were 45, 38 and 25 patients who developed distant metastasis (DM) in Arms 1, 2 and 3. The HR was 0.52 (95% CI: 0.32-0.85) for Arm 3 vs Arm 1 and 0.64 (95% CI: 0.39-1.06) for Arm 3 vs. Arm 2. With IMRT use in 87% of cases, there were no significant differences in late grade 2+ or 3+ renal/GU or GI events; only grade 2+ blood/bone marrow events attributable to PLNRT were significant (p<0.044). CONCLUSIONS: These are the first randomized findings to demonstrate that extending salvage radiotherapy to cover the pelvic lymph nodes results in early, meaningful, reductions in progression when combined with STAD. Follow-up of patients will further elucidate the magnitude of the differences in DM and in FFP between arms 2 and 3. Source of Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), U24CA180803 (IROC) from the National Cancer Institute (NCI)