An Update of the Phase III Trial Comparing Whole-Pelvic (WP) to Prostate Only (PO) Radiotherapy and Neoadjuvant to Adjuvant Total Androgen Suppression (TAS): Updated Analysis of RTOG 94-13

Purpose/Objective: This trial was designed to test the hypothesis that TAS and WP radiotherapy (RT) followed by a prostate boost improves the progression-free survival (PFS) by at least 10% compared to TAS and PO RT. This trial was also designed to test the hypothesis that neoadjuvant hormonal therapy(NHT) followed by concurrent TAS and RT improves the PFS compared to RT followed by adjuvant TAS (AHT) by at least 10%. Materials/Methods: Patients eligible for the study included those with clinically localized adenocarcinoma of the prostate and an elevated prostate specific androgen (PSA) < 100ng/ml. Patients were stratified by T stage, PSA, and Gleason score (GS) and required to have an estimated risk of lymph node (LN) involvement > 15% based on the equation +LN = (2/3) PSA + (GS-6) × 10. TAS consisted of an LHRH agonist (Leuprolide or Goserelin) and Flutamide 250 mg p.o. tid administered two months before and during RT (NHT) or for four months following the completion of RT (AHT). Accrual of 1,323 cases occurred between April 1, 1995 and June 1, 1999. Three hundred and thirty two, 331, 329, and 331men were randomized to WP RT + NHT, PO RT + NHT, WP RT + AHT, and PO RT + AHT respectively. 73% of patients had a Gleason score > 7, median PSA was 23ng/ml and 67% of patients had > T2c disease. The study design resulted in a balance between all four arms for clinical stage, GS, PSA, and estimated risk of lymph node involvement. PSA failure was defined as two consecutive rises or a PSA > 4ng/ml at the last follow up after the PSA nadir value was reached. Results: With a median follow up since study entry for all patients of 5.9 years, patients treated with WP RT + NHT in pair wise comparison analysis show a statistically significant difference in PFS over PO RT +NHT (p=0.0041) and a statistically significant improvement over WP RT + AHT (p=0.0045). WP RT + NHT shows a trend in progression free survival over PO RT + AHT (p= 0.0656). Five year PFS for WP RT + NHT, PO RT + NHT, WP RT + AHT and PO RT + AHT is 48.3%, 36.8%, 38.1%, and 40.4% respectively. Biochemical failure was also statistically significantly improved in pair wise comparison analysis for WP RT + NHT versus PO RT + NHT (p=0.0070), WP RT + NHT versus WP RT + AHT shows a trend towards significance with a (p=0.0699). WP RT + NHT versus PO RT + AHT was not statistically different regarding protocol definition of biochemical failure (p=0.2181). The five year biochemical failure rate for WP RT + NHT, PO RT + NHT, WP RT + AHT, and PO RT + AHT were 35.9%, 45.5%, 42.8%, and 40.0% respectively. To date no overall survival advantage has been seen. At five years overall survival for WP RT + NHT, PO RT + NHT, WP RT + AHT, and PO RT + AHT are 81.6%, 77.8%, 75.5%, and 81.2% respectively. Conclusions: This updated analysis reveals that WP RT + NHT is associated with improved PFS over PO RT + NHT and WP RT + AHT and trends toward improved PFS over PO RT + AHT. WP RT + NHT is associated with improved biochemical failure over PO RT + NHT, marginal improvement over WP RT + AHT, but may not be different from PO RT + AHT. Longer follow up is needed to confirm the benefit of these findings in regards to overall and cause specific survival.