Cedars-Sinai Medical Center, Los Angeles, CA
Howard M. Sandler , Theodore Karrison , A. Oliver Sartor , Leonard G. Gomella , Mahul B. Amin , James Purdy , Jeff M. Michalski , Mark Garzotto , Nadeem Pervez , Alexander G. Balogh , George Rodrigues , Luis Souhami , M. Neil Reaume , Scott Williams , Raquibul Hannan , Christopher U. Jones , Eric M. Horwitz , Joseph P. Rodgers , Felix Y Feng , Seth A. Rosenthal
Background: High-risk, localized prostate cancer has a poor prognosis. We hypothesized that adj docetaxel (D) and prednisone and long-term (24 mos) androgen suppression (AS) and radiation therapy (RT) would improve overall survival (OS) and tested this in NRG/RTOG 0521. Results with med follow-up of 5.7 yrs were reported (JCO 37:1159, 2019), showing a benefit of D (HR=0.69, 90% CI: 0.49-0.97, 1-sided p=0.034). Med follow-up is now 10.4 yrs and we report updated results for OS and metastasis (DM). Methods: NRG/RTOG 0521 opened 12/05 and closed 8/09 with targeted accrual of 600 and designed to detect a HR of 0.49, based on improvement in 4-yr OS from 86 to 93%. With 0.05 1-sided type I error and 90% power >78 deaths were required. Pts were stratified by predefined risk groups. Group 1: Gl 9-10, any T; Group 2: Gl 8, PSA<20, T≥T2; Group 3: Gl 8, PSA≥20, any T; Group 4: Gl 7, PSA≥20, any T. maxPSA ≤150. RT dose was 75.6 Gy. Chemo consisted of 6, 21-day cycles of D starting 28 days after RT. Results: Of 612 accrued, 563 were eligible/available for analysis. By risk group 1-4, there were 297, 116, 64, and 86 pts. Med PSA 15 ng/mL. 10-yr OS rates were 64% [95% CI: 58-70%] for AS+RT and 69% [95% CI: 63-75%] for AS+RT+CT (HR = 0.89, 90% CI: 0.70, 1.13, 1-sided p=0.22). However there was evidence of non-proportional hazards (Grambsch-Therneau test, p=0.016). Thus survival was alternatively evaluated with restricted mean survival time (RMST). The difference in RMST at 10 yrs was 0.42 yrs (90% CI: 0.07-0.77, 2-sided p=0.048). Cumulative incidence of DM at 10 yrs was 22% [95% CI: 17-27%] for AS+RT and 20% [95% CI: 15-25%] for AS+RT+CT (2-sided log-rank p=0.29). At 10 years most deaths occurred in risk group 1: 62 in AS+RT and 50 in AS+RT+CT (HR= 0.93, 95% CI: 0.66-1.32, 2-sided log-rank p=0.16). There was no new related Grade 5 toxicity. Conclusions: OS findings, reported after follow-up of 5.7 yrs, demonstrated a small beneficial effect of adding D to AS and RT. With longer follow-up the benefit of D remains, but the HR varies over time and the OS curves have converged. Support: U10CA180868 (NRG Operations), U10CA180822 (NRG SDMC), U24CA180803 (IROC) from the NCI and Sanofi-Synthelabo Int. Clinical trial information: NCT00288080
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