A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

Abstract

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.

Docetaxel-titanate nanotubes enhance radiosensitivity in an androgen-independent prostate cancer model

“…17 Several trials have evaluated tolerance to DTX combined with hormonal therapy and RT for high-risk PCa. 2,18,19 The results of a Phase II trial showed that although feasible, 30% of Grade 3 or higher toxicities was observed. 2 More recently, the GETUG-12 trial found improved relapsefree survival with sequential DTX combined with HT and RT compared with HT alone.…”

The very-high-risk prostate cancer: a contemporary update

“…Furthermore, the trial was terminated prematurely due to a high rate of thromboembolic events in the chemotherapy arm. 88 Contrary, contemporary studies demonstrated a possible benefit favoring the use of chemotherapy. 75,90,91 In a subset of patients with non-metastatic high risk locally advanced tumors comprising part of the STAMPEDE cohort, docetaxel improved failure-free survival (HR 0.60, 95% CI 0.45–0.80; p<0.001); however, OS analyses were underpowered.…”

“…75,88-91 The RTOG 9902 trial assessed whether the addition of paclitaxel, estramustine, and oral etoposide would improve survival in high-risk prostate cancer patients treated with combined RT and long term ADT. The 10-year results revealed no difference in outcome, controlling for tumor stage, Gleason score, and pre-treatment PSA.…”

Inclusiveness and ethical considerations for observational, translational, and clinical cancer health disparity research

“…The NCTN/NCORP data set is a convenience sample of clinical trial data submitted to the NCTN from studies published after 2015. For all tumor types (except pancreas), publications from 21 clinical trials reported to NCTN/NCORP were reviewed for race/ethnic status (Table ).…”