106 - Long-Term Follow-up Results for NRG/RTOG 0815: A Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy with or without Short-Term Androgen Deprivation Therapy for Patients with Intermediate-Risk Prostate Cancer
Presenter(s)
D. J. Krauss1, T. G. Karrison2, A. A. Martinez3, G. Morton4, D. W. Bruner5, M. A. Elshaikh6, D. Yan7, B. Movsas6, D. E. Citrin8, A. Jani9, J. M. Michalski10, J. A. Efstathiou11,12, A. D. Currey13, A. L. Chen14, F. L. Cury15, M. Mohiuddin16, A. Raben17, T. Johnson18, P. L. Nguyen19, and H. M. Sandler20; 1Department of Radiation Oncology, Corewell Health Beaumont University Hospital, Royal Oak, MI, 2NRG Oncology SDMC, Philadelphia, PA, 3GenesisCare USA, Fort Myers, FL, 4Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 5Emory University Hospital/Winship Cancer Institute, Atlanta, GA, 6Department of Radiation Oncology, Henry Ford Health, Detroit, MI, 7West China Hospital of Sichuan University, Chengdu, China, 8Center for Cancer Research at the National Cancer Institute, Bethesda, MD, 9Department of Radiation Oncology, Emory University, Atlanta, GA, 10Washington University School of Medicine, St. Louis, MO, 11Department of Radiation Oncology, Mass General Brigham Cancer Institute, Boston, MA, 12Massachusetts General Hospital, Boston, MA, 13Department of Radiation Oncology Medical College of Wisconsin, Milwaukee, WI, 14Texas Oncology Cancer Center Sugar Land, Sugar Land, TX, 15McGill University, Montreal, Canada, 16Saint John Regional Hospital and Dalhousie University, Saint John, NB, Canada, 17Christiana Care Health System, Newark, DE, 18American College of Radiology, Philadelphia, PA, 19Mass General Brigham Cancer Institute, Boston, MA, 20Oregon Health and Science University, Portland, OR
Purpose/Objective(s): Initial reported results of NRG/RTOG 0815 demonstrated reductions in rates of biochemical and local failure as well as distant metastases for patients receiving short-term androgen deprivation (STAD) in addition to dose-escalated radiotherapy (RT) compared to dose-escalated RT alone. However, the study did not demonstrate a significant benefit to adding STAD with respect to overall survival. Updated clinical results with extended follow-up are presented here.
Materials/Methods: Eligible patients had intermediate risk prostate cancer defined by the presence of > 1 of the following features: clinical stage T2b-T2c, Gleason score 7, or baseline PSA > 10 and < 20 ng/mL. Patients were stratified by the presence of 1 vs. > 1 intermediate risk factor, baseline ACE-27 comorbidity score (> 2 vs. < 2), and RT boost modality. Randomization was to dose-escalated RT alone (Arm 1) or combined with STAD consisting of LHRH agonist/antagonist plus oral anti-androgen for 6 months (Arm 2). RT was administered per the discretion of the treating physician and consisted of external beam RT (EBRT) alone to 79.2 Gy or EBRT (45 Gy) combined with LDR or HDR brachytherapy boost. The primary endpoint was overall survival.
Results: The study accrued 1538 patients between 2009-2016 with 1493 eligible for analysis, 751 on Arm 1 and 742 on Arm 2. Baseline clinical characteristics were well-balanced between treatment arms. 88% of patients were treated with dose-escalated EBRT alone, 67% had a single intermediate risk factor, and 67% an ACE-27 score < 2. Median follow-up was 9.4 years (10.3 years for surviving patients). No differences in rates of late Grade > 3 adverse events were observed between treatment arms. 446 deaths occurred, 239 in Arm 1 and 207 in Arm 2, corresponding to 14-year overall survival rates of 53% vs. 58% (HR 0.87, 95% CI: 0.72-1.04, p = 0.13). Rates of biochemical failure (HR 0.60, p < 0.001) and local failure (HR 0.44, p < 0.001) were lower in Arm 2. 40 patients developed distant metastases on Arm 1 compared to 14 on Arm 2 (HR 0.35, p < 0.001). Metastasis-free survival at 14 years was 50% for Arm 1 vs. 57% for Arm 2 (HR 0.83, p = 0.042). 19 deaths were attributed to prostate cancer on Arm 1 compared to 5 on Arm 2 (HR 0.26, p = 0.004). No significant difference in non-prostate cancer-related mortality was observed.
Conclusion: The addition of STAD to dose-escalated RT resulted in improvements in clinical failure rates, prostate cancer-specific mortality, and metastasis-free survival. No statistically significant benefit in overall survival was found.