Noninferiority of hypofractionated vs conventional postprostatectomy radiotherapy for genitourinary and gastrointestinal symptoms: The NRG-GU003 phase 3 randomized clinical trial


Mark K. Buyyounouski, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
Ronald C. Chen, University of Kansas Cancer Center, Kansas City.
Mark J. Mann, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Rajat J. Kudchadker, MD Anderson Cancer Center, The University of Texas, Houston.
Andre A. Konski, University of Pennsylvania, Philadelphia.
Omar Y. Mian, Cleveland Clinic Foundation, Cleveland, Ohio.
Jeff M. Michalski, Washington University School of Medicine in St Louis, St Louis, Missouri.
Eric Vigneault, Radiation Oncology, CHU de Québec-Hôpital Enfant Jésus de Quebec, Quebec City, Quebec, Canada.
Richard K. Valicenti, University of California, Davis Comprehensive Cancer Center, Sacramento.
Maroie Barkati, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Colleen A. Lawton, Medical College of Wisconsin, Milwaukee.
Louis Potters, Northwell Health NCORP, Lake Success, New York.
Drew C. Monitto, Upstate Carolina Consortium Community Oncology Research Program, Spartanburg, South Carolina.
Jeffrey A. Kittel, Advocate Health - MidwestFollow
Thomas M. Schroeder, New Mexico Minority Underserved NCORP, Albuquerque.
Raquibul Hannan, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas.
Casey E. Duncan, Heartland Cancer Research NCORP, Decatur, Illinois.
Joseph P. Rodgers, NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
Felix Feng, University of San Francisco, San Francisco, California.
Howard M. Sandler, Cedars-Sinai Medical Center, Los Angeles, California.


Importance:No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective:To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants:In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (

Intervention:Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures:The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events.

Results:Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28).

Conclusions and relevance:In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy.



PubMed ID