The secondary quality of life (QOL) results of NRG GU-005 were presented in the September 29 afternoon Plenary Session by Rodney Ellis, MD, University of South Florida. Dr. Ellis presented results from “Co-Primary Results from NRG-GU005 An International Phase III Trial of SBRT vs. Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer. This randomized phase III superiority trial tested if SBRT is superior to hypofractionated IMRT for patient-reported GI and GU toxicity, as measured by EPIC-26 bowel and urinary irritation domains at two years, and if SBRT is superior to hypofractionated IMRT for disease free survival (DFS) at five years. With 698 patients, the study was 80% powered to demonstrate superiority for QOL endpoints and 89% powered to demonstrate superiority for DFS.
Patients were on average 68 years of age with 94% having Gleason 7 prostate cancer, 82% T1 disease, and a median PSA of 7.0 (max 19.7). The CTV was the prostate +/- proximal seminal vesicles with MRI planning and fiducial markers required. PTV margins were 8 mm (5 mm posterior) for MH-IMRT and 5 mm (3 mm posteriorly) for SBRT. SBRT entailed (36.25 Gy/5 fractions) while moderately hypofractionated IMRT (MH-IMRT) utilized (70 Gy/28 or 60 Gy/20). Notably 60% of men had rectal spacers and/or balloons.
At two years, bowel QOL favored SBRT with 35% having a decline meeting minimal clinically significant difference (MCD) as compared to 44% with MH-IMRT (p=0.034), but there was no difference in declines in urinary obstructive QOL (35% SBRT v. 34% MH-IMRT, p=0.68). For DFS the futility bound was crossed, leading to early reporting of the trial. A 30% improvement in DFS was hypothesized for SBRT, which was ruled out with five-year DFS of 89% (95%CI: 85-92) for SBRT and 92% (95%CI:89-95) for MH-IMRT. The difference in DFS was largely driven by an increase in BF with SBRT [3-years: 8% (95%CI: 5.2-11.0) v. 4% (95%CI:2.3-7.0), p=0.037]. One additional finding was that rectal spacers were associated with less likelihood of having a decline in bowel QOL for both MH-IMRT and SBRT (p=0.001).
Dr. Ellis noted that this study met its first co-primary endpoint with lower declines in bowel QOL with SBRT as compared to MH-IMRT while not reaching the urinary obstructive endpoint. Notably, urinary incontinence, however, was reduced with SBRT. Nevertheless, the second co-primary endpoint of DFS was not superior with SBRT, and in fact, BF was worse with SBRT as compared to MH-IMRT. In contrast, the PACE-B randomized trial used 40 Gy to the PTV (a 19% increase in BEDα/β2) and found an increase in urinary toxicity without a change in bowel toxicity or BF. As such, small differences in dose could have noticeable impacts. In addition, it is unclear what differences in margin size between arms (8 v. 5 mm) had. Finally, Dr Ellis noted that dominant nodule boosts as used in the FLAME and HYPO-FLAME studies may improve BF without an increase in toxicity but were not allowed in this study. As such GU-005 provides another piece in the understanding of SBRT for prostate cancer.
Abstract 1 - Co-Primary Results from NRG-GU005 An International Phase III Trial of SBRT vs. Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer was presented in Plenary Session during ASTRO’s 67th Annual Meeting.
Read additional commentary from Dr. Hamstra on the NRG: GU005 QOL results.
