Long-Term Outcomes of NRG/RTOG 0126, a Randomized Trial of High Dose (79.2 Gy) vs. Standard Dose (70.2 Gy) Radiation Therapy (RT) for Men with Localized Prostate Cancer

Abstract

NRG/RTOG 0126, a phase III trial for men with localized prostate cancer testing whether dose escalation to 79.2 Gy with 3DCRT/IMRT improved overall survival (OS). Long-term results of this trial are presented. Patients with clinical stage T1b-T2b and either Gleason Score (GS) 2-6 and 10 ≤ PSA < 20 or GS 7 and PSA < 15 were eligible and randomized to receive 79.2 Gy or 70.2 Gy. No previous or concurrent androgen withdrawal therapy was administered. Treatment was delivered with 3DCRT/IMRT to a dose of 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions to the PTV encompassing the prostate and seminal vesicles. Image guidance was not required. ASTRO and Phoenix definitions were used for biochemical failure (ABF and PBF, respectively). OS was estimated by the Kaplan-Meier method and arms compared with the log-rank test. ABF, PBF, local progression (LP), distant metastases (DM) and time to late GI/GU toxicities were estimated by the cumulative incidence method and arms compared with Gray's test. One thousand five hundred thirty-two men were randomized, 763 to 79.2 Gy and 769 to 70.2 Gy. 1499 were eligible, 748 and 751 in the 79.2 Gy and 70.2 Gy arms respectively. Median age was 71, 70% had PSA < 10 ng/ml, 84% with GS 7, 57% had T1 disease, and 66% treated with 3D-CRT. Outcomes are shown in the TABLE: . With a median follow up of 12 years, there was no significant difference in OS. There was a statistically significant decrease in the cumulative incidence of ABF, PBF, DM, LP, and salvage therapies in the 79.2 Gy arm. There were significantly higher rates of grade 2+ GI and GU toxicity in the 79.2 Gy arm. There were no statistically significant differences in the rates of grade 3+ GU or GI toxicity between either arm. Long term follow up confirms no improvement in OS with dose escalation in this study population. However, there are significant improvements in ABF, PBF, DM, LP, and need for salvage therapy. Despite the use of more salvage therapy in the low dose arm, dose escalated RT resulted in lower rates of DM, a clinically relevant endpoint. Patients receiving dose escalation do experience a higher rate of grade 2+ GU and GI toxicity but no worse grade 3+ toxicities.