1 - Primary Results from NRG-GU005: A Phase III Trial of SBRT vs. Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer
Presenter(s)
R. J. Ellis III1, S. Pugh2,3, J. B. Yu4, F. Y. Feng5, A. A. Konski6, R. Grubb7, R. E. Wallace8, D. J. Gladstone9, C. Menard10,11, A. J. Frazier12, J. D. Pennington13, J. M. Michalski14, D. E. Spratt15, A. A. Martinez16, S. C. Morgan17, A. M. Mihai18, R. Paulus19, and H. M. Sandler20; 1University of South Florida/Tampa GeneralHospital, Tampa, FL, 2NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 3The American College of Radiology, Philadelphia, PA, 4Department of Radiation Oncology and Applied Sciences, Dartmouth Geisel School of Medicine, Lebanon, NH, 5University of California at San Francisco, San Francisco, CA, 6Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 7Medical University of South Carolina, Charleston, SC, 8Cedars-Sinai Medical Center, Los Angeles, CA, 9Geisel School of Medicine at Dartmouth & Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH, 10Département de radio-oncologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada, 11Department of radiation oncology, CHUM, Montreal, QC, Canada, 12McLaren Cancer Institute-Macomb, Mount Clemens, MI, 13Southeast Clinical Oncology Research Consortium NCORP, Winston Salem, NC, 14Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 15Case Western Reserve University, Cleveland, OH, 16GenesisCare USA, Fort Myers, FL, 17The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada, 18Beacon Hospital and Cancer Trials Ireland, Dublin, Ireland, 19The American College of Radiology, Philidelphia, PA, 20Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): This randomized non-blinded phase III trial compared stereotactic body radiation therapy (SBRT) to moderately hypofractionated intensity-modulated radiation therapy (M-IMRT) in localized intermediate risk prostate cancer patients and was designed for superiority of disease-free survival (DFS) and patient-reported health related quality of life (HRQOL).
Materials/Methods: The NRG-GU005 trial enrolled patients with intermediate-risk prostate cancer and were randomized 1:1 to receive SBRT (36.25 Gy in 5 fractions) or IMRT (70 Gy in 28 fractions or 60 Gy in 20 fractions). The HRQOL co-primary endpoint was designed to show 10% and 8% absolute reductions in the frequency of a minimal clinically important decline (MCID) in bowel and urinary irritation/obstruction (UIO) domains, respectively, at 24 months. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was administered at baseline, 12- and 24-months post-treatment. MCID was defined as =4 points for EPIC bowel and =5 points for UIO symptoms compared to baseline. The DFS endpoint, defined as time to biochemical (Phoenix definition), local, or regional failure, distant metastasis, or death from any cause, was designed to detect a 38% relative improvement with SBRT. Both endpoints had interim futility analyses.
Results:
A total of 698 patients were randomized, with 353 in the SBRT arm and 345 in the IMRT arm. At 2 years post-treatment, 82.5% of MH-IMRT and 85.1% SBRT patients completed the EPIC-26. Of those, 97.5% and 96.2% had scorable bowel and UIO domains. Baseline characteristics and bowel and UIO domains were balanced between groups. There were significantly fewer patients in the SBRT arm who experienced a 2-year MCID in bowel HRQOL (34.9% vs. 43.8%, p=0.034). MCID frequency for the UIO domain was not significantly different between SBRT and IMRT (33.7% vs. 34.7%, p=0.68). The analysis of the longitudinal bowel domain scores showed a significant treatment effect in favor of SBRT (least square [LS] mean=2.68, 95% CI: 1.02, 4.34; p=0.0016). Using a rectal spacer occurred in 56% SBRT vs 55% IMRT subjects and resulted further in superior EPIC bowel domain scores (LS mean=-2.81, 95% CI: -4.49, -1.13; p=0.0011). The futility bound for DFS was crossed in the interim analysis, indicating lack of superiority for SBRT over hypofractionated IMRT (3-year rates of 88.6%, 95% confidence interval [CI]: 85.2-92.1 for SBRT vs. 92.1%, 95% CI: 88.9-95.2for IMRT). Minimal local or distant failures were reported, however cumulative instance of biochemical failure was lower at 3 years in IMRT as compared to SBRT (4.2%, 95% CI: 2.3-7.0 vs. 7.8%, 95% CI: 5.2-11.0, p=0.0367).Conclusion:
SBRT to a dose of 36.25 Gy resulted in favorable bowel HRQOL based on patient reported outcomes compared to M-IMRT. Urinary HRQOL was not significantly different. At 36.25 Gy, there was a lack of improvement in DFS for SBRT over IMRT.