108 - Three-Year Outcomes of a Prospective Randomized Trial of Moderately-Hypofractionated and Standard-Fractionated Proton Therapy in Prostate Cancer Embedded within COMPPARE Trial
Presenter(s)
N. P. Mendenhall1, C. M. Bryant1, R. C. Chen2, C. G. Morris1, A. M. Crisp3, R. H. Henderson1, W. M. Mendenhall1, C. C. Sinesi4, I. C. Namihas Jr5, B. R. Jabola5, R. C. Nichols Jr1, H. Mok6, S. Choi7, H. E. Gayar8, C. Hyde9, B. S. Hoppe10, J. Kang11, and J. D. Slater5; 1Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL, 2Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, 3Center for Data Solutions, University of Florida College of Medicine Jacksonville, Jacksonville, FL, 4Hampton University Proton Therapy Institute, Hampton, VA, 5Department of Radiation Medicine, Loma Linda University School of Medicine, Loma Linda, CA, 6Department of Genitourinary Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7Department of Genitourinary Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 8McLaren Regional Medical Ctr, Flint, MI, 9Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 10Mayo Clinic, Department of Radiation Oncology, Jacksonville, FL, 11Providence Affiliated Physicians, Los Angeles, CA
Purpose/Objective(s): To fill an evidence gap on non-inferiority of moderately-hypofractionated (MF) proton therapy (PT) compared with standard fractionated (SF) PT in prostate cancer, a prospective randomized trial was embedded within COMPPARE, a multi-institutional Prospective Comparison of Outcomes with Proton and Photon Radiation in Prostate Cancer. We hypothesize MFPT is non-inferior to SFPT in localized prostate cancer with respect to bowel function, gastrointestinal toxicity, and freedom from biochemical disease progression (FFBP).
Materials/Methods: Between 2018-2022, 2524 patients were enrolled in the COMPPARE trial including 1501 treated with PT. A randomized controlled trial comparing 60 Gy(RBE) in 20 fractions (n=299) and 78 Gy(RBE) in 39 fractions (n= 301) was nested within the PT cohort. Median age was 68, 77% of patients had PSA <10, 94.5% had Gleason 6-7, 16.6% were Black, 90.5% had rectal spacers, 39.1% received androgen deprivation therapy and 75% had Medicare/Medicaid coverage. Twenty-four patients were screen failures after randomization, and 23 more were withdrawn prior to reaching the 3-year timepoint leaving 553 analyzable patients at three years. Two hundred and seventy-seven received 60 Gy in 20 fractions and 276 received 78 Gy(RBE) in 39 fractions. Median follow-up for these 553 patients is 4.1 years. The primary endpoints were moderate or big problems (scores of 3 or 4) on the bowel urgency and bowel frequency questions from the Expanded Prostate Index Composite (EPIC) questionnaire at 3 years. MFPT and SFPT patients were both assumed to have a 7% rate of moderate or big problems with bowel urgency with a 6% non-inferiority margin while a 4% rate with a 4.5% non-inferiority margin was assumed for bowel frequency. Secondary endpoints were = Grade 2 gastrointestinal toxicity scored by the CTCAEv5.0, and FFBP.
Results: For MFPT and SFPT at 3 years, EPIC bowel summary score medians were 96.4 and 94.6 [95% confidence interval (CI): -1.39-1.70] respectively, moderate to big problems (score 3 or 4) in bowel urgency were reported in 4.1% and 7.9% (95% CI: -1.40-0.77), moderate to big problems (score of 3 or 4) in bowel frequency were reported in 2.5% and 4.6% (95% CI: -1.35-1.10), the incidences of Grade = 2 gastrointestinal toxicity were 4.4% and 4.8% [Hazard ratio (HR): 1.06, 95% CI: 0.49-2.33 when controlling for rectal spacers], and FFBP rates were 97.8% and 99.25% (HR: 1.76, 95% CI: 0.52-5.93).
Conclusion: We have established that MFPT is non-inferior to SFPT at 3 years with respect to gastrointestinal function. There was also no significant difference between MFPT and SFPT with respect to gastrointestinal toxicity and FFBP. Longer follow-up is needed to verify non-inferiority of late outcomes including second malignancy.