7 - Five-Year Results of a Phase 3 Trial of Hypofractionated vs. Conventional Postprostatectomy Radiotherapy: NRG Oncology GU003
Presenter(s)
M. K. Buyyounouski1, M. Borges2, R. C. Chen3, M. Mann4, R. Kudchadker5, A. A. Konski6, R. D. Tendulkar7, J. M. Michalski8, E. Vigneault9, J. M. Kilburn10, R. K. Valicenti11, L. Potters12, A. D. Currey13, M. Barkati14, T. M. Schroeder15, J. Kittel16, N. B. Desai17, S. Pugh2, P. L. Nguyen18, and H. M. Sandler19; 1Stanford University, Stanford, CA, 2NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 3Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, 4Summit Health, Millburn, NJ, 5MD Anderson Cancer Center, Houston, TX, 6Chester County Hospital, West Chester, PA, 7Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, 8Washington University School of Medicine, St. Louis, MO, 9Centre Intégré Cancérologie et Centre de recherche CHU de Québec Université Laval, Quebec City, QC, Canada, 10Spartanburg Medical Center, Spartanburg, SC, 11UC Davis Comprehensive Cancer Center, Sacramento, CA, 12Northwell Health NCORP, Lake Success, NY, 13Department of Radiation Oncology Medical College of Wisconsin, Milwaukee, WI, 14CHUM - Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada, 15University of New Mexico, Albuquerque, NM, 16Aurora NCI Community Oncology Research Program - Aurora St. Luke’s Medical Center, Milwaukee, WI, 17University of Texas Southwestern Medical Center, Dallas, TX, 18Mass General Brigham Cancer Institute, Boston, MA, 19Oregon Health and Science University, Portland, OR
Purpose/Objective(s):
Biopsy Gleason 8–10 disease and MRI-suspected extracapsular extension identify men at high risk for adverse pathologic features at prostatectomy, observed in ~55–75% of cases. For a substantial subset, surgery alone is not curative, and PSA recurrence leads to radiotherapy (RT) to preserve curative intent. Conventionally fractionated postprostatectomy RT (COPORT) requires 37 fractions, 48% more than hypofractionated RT (HYPORT). In the primary 2-year analysis of this trial, HYPORT was noninferior to COPORT for patient-reported genitourinary and gastrointestinal toxicity. We now report longer-term 5-year results.
Materials/Methods:
A total of 296 men were randomized (152 to COPORT and 144 to HYPORT). Men with a detectable post-op PSA (=0.1 ng/mL) with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 or pT2 disease with a positive surgical margin were eligible. HYPORT was 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT was 66.6 Gy in 37 fractions of 1.8 Gy. Patient-reported GU and GI toxicity was measured using the Expanded Prostate Index Composite (EPIC). Other secondary endpoints include quality of life as measured by EQ-5D, adverse events (AEs), overall survival, prostate-cancer specific survival, and biochemical failure (BF; PSA = 0.4 ng/mL and rising).
Results:
No grade 4–5 AEs related to RT were reported. Grade 3 AEs occurred in 7% (11 men) with COPORT and 16% (23 men) with HYPORT (p=0.02). Grade 3 renal and urinary disorders occurred in 3% (5 men) with COPORT and 13% (18 men) with HYPORT (p=0.003). This difference reflected higher rates of noninfective cystitis (0% vs 7%) and hematuria (0.7% vs 6%) with HYPORT vs COPORT. There was only one grade 3 urinary tract obstruction (stricture) on the COPORT arm. Time to grade 3 AEs did not differ between arms (p=0.4).
At 5 years, EPIC compliance was 56% (58% in the COPORT arm and 55% in the HYPORT arm), while EQ-5D compliance was 51% in both arms. No significant differences were observed in 5-year EPIC bowel (0.6 vs -2.0; p=0.1) or urinary change scores (-5.7 vs -8.0; p=0.4) between COPORT and HYPORT. No significant difference was observed in EQ-5D score change from baseline to 5 years between COPORT and HYPORT (-0.01 vs 0.0; p=0.5).
Median follow-up is 7 years (range: 0 to 8). A total of 31 deaths have been reported (14 on COPORT and 17 on HYPORT), 4 (13%) due to prostate cancer. There was no difference in BF (5-year rate: 18% for COPORT vs. 21% for HYPORT; p=0.3).
Conclusion:
The rates of grade 3 GU AEs (3% with COPORT and 13% with HYPORT), including the higher incidence with HYPORT and the predominance of cystitis and hematuria, were consistent with contemporary series. Despite a small absolute increase in physician-reported cystitis (7%) and hematuria (5%), HYPORT showed no differences in patient-reported outcomes compared with COPORT and comparable biochemical control, supporting HYPORT as an effective, patient-centered, and acceptable treatment approach.