NRG Oncology/RTOG 0415, Hypofractionation in Patients with Low-Risk Prostate Cancer: Are Patient Reported Outcomes the Practice Change Tipping Point?
Pugh SL, Lee WR, Dignam J, Low D, Swanson GP, Shah AB, D'Souza DP, Michalski JM, Dayes IS, Seaward SA, Nguyen PL, Hall WA, Pisansky TM, Chen Y, Sandler HM, Movsas B, and Bruner DW. NRG Oncology/RTOG 0415, hypofractionation in patients with low-risk prostate cancer: Are patient reported outcomes the practice change tipping point? Quality of Life Research 2017; 26(1):38-39.
Qual Life Res
Aims: Hypofractionated radiation therapy (H-RT) is non-inferior to conventional (C-RT) fractionation schedules in men with low- or intermediate-risk prostate cancer as shown in three large randomized trials including 0415. However, 0415 had a 6.9% higher rate of physician reported GI grade 2 (but not grade 3+GI or any GU) adverse events on the H-RT arm. This study assessed differences in patient reported outcomes (PROs) between H-RT and C-RT in men with lowrisk prostate cancer enrolled on 0415. Methods: Eligibility included men with low-risk prostate cancer randomly assigned to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). PROs were assessed with the Expanded Prostate Index Composite (EPIC) and two additional instruments new to this report, the Hopkins Symptom Checklist (HSCL), a measure of anxiety and depression, and EQ-5D (a generic index of health status and utilities) collected at baseline, and at 6, 12, 24, and 60 months thereafter. Change scores, calculated as follow-up - baseline score were compared between treatment arms. Clinical significance was determined for EPIC change scores determined by published recommendations of 0.5 effect size. Results: Of 1092 patients analyzable for the 0415 primary endpoint, 962 consented to PROs. No statistically significant differences related to any PRO baseline scores were measured between treatment arms. There were no differences in change scores between arms with respect to any EPIC domain (bowel, bladder, sexual) except at 12 months, when patients assigned H-RT reported greater decline in bowel domain compared with C-RT (median score -3.6 vs. -1.8, respectively, p = 0.0037), but it did not reach clinical significance. There were no between-group difference at any time point for the HSCL or EQ-5D. Conclusions: The current study shows that patients assigned H-RT did not have clinically significant decline in self-reported bowel, bladder, or sexual quality of life, or in occurrence of anxiety or depression, with utility scores comparable to C-RT. These findings add weight to the clinical outcomes supporting the generalized use of H-RT as best medical practice for men with low- or intermediate-risk prostate cancer.