A Phase III trial of 2 Years of Androgen Suppression (AS) and Radiation Therapy (RT) with or without Adjuvant Chemotherapy (CT) for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group (RTOG) Phase III Randomized Trial NRG Oncology RTOG 9902
Mené sur 380 patients atteints d'un cancer de la prostate à risque élevé de récidive (durée médiane de suivi : 9,2 ans), cet essai de phase III évalue, du point de vue de la survie sans maladie et de la survie globale, l'intérêt d'ajouter une chimiothérapie adjuvante par paclitaxel-estramustine-étoposide à une radiothérapie en combinaison avec un traitement anti-androgénique d'une durée de deux ans
Purpose : Long-term (LT) androgen suppression (AS) with RT is a standard treatment for high-risk, localized prostate cancer (PCa). RTOG 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide (TEE) + LT AS+ RT would improve overall survival (OS). Materials and Methods : High-Risk PCa patients (PSA 20-100 and Gleason score (GS) ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS+RT) alone or with adjuvant CT (AS+RT+CT). CT was four 21-day (d) cycles, delivered beginning 28d after 70.2 Gy RT. AS was: LHRH for 24 months (mo) beginning 2 mo prior to RT plus oral anti-androgen for 4 mo before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results : 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% having Gleason Score 8-10, and 34% T3-T4 tumors, and median PSA of 22.6 ng/ml. Median follow-up is 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. 10-year results for all randomized patients revealed no significant difference in AS+RT vs. AS+RT+CT in OS (65% vs. 63%; p=0.81); Biochemical Failure (BF) (58% vs. 54%; p=0.82); Local Progression (LP) (11% vs. 7%; p=0.09); Distant Metastases (DM) (16% vs. 14%; p=0.42); or Disease-Free Survival (DFS) (22% vs. 26%; p=0.61). Conclusions : NRG Oncology RTOG 9902 showed no significant difference in OS, BF, LP, DM, or DFS with the addition of adjuvant CT to LT AS + RT. The trial provides valuable data regarding the natural history of high-risk PCa treated with LT AS + RT, and has implications for the feasibility of clinical trial accrual and tolerability utilizing CT in PCa.
http://www.redjournal.org/article/S0360-3016%2815%2900552-0/abstract