Impact of rectal spacer on toxicity reduction in men treated with proton versus photon therapy.

Abstract

247 Background: Dose escalation in prostate cancer (PCa) radiotherapy (RT) is limited by toxicity to surrounding tissue, including the rectum. Rectal spacers improve bowel toxicity in men treated with photons (i.e. IMRT). However, the relative benefit of rectal spacers in men treated with protons remains unknown. Further, proton therapy may result in high-dose exposure to the anterior rectal wall due to lateral penumbra with conventional opposed lateral beam arrangement. We hypothesize that rectal spacers will confer greater toxicity benefit in the setting of proton therapy compared with photon therapy. Methods: We conducted an IRB approved, single institution, retrospective review of patients receiving definitive conventional or moderate hypofractionated photon IMRT or pencil-beam scanning proton RT for localized PCa from 2018-2021. Four cohorts were compared: Photon with (Ph+RS) or without (Ph-RS) rectal spacer, and proton with (Pr+RS) or without (Pr-RS) rectal spacer. Rates of pelvic nodal treatment were equivalent between protons and photons within the +/- rectal spacer cohorts. Acute (<3 months) and late (≥ 3 month) toxicity was compared amongst the four cohorts. Cumulative incidence of physician-reported grade 1-2 gastrointestinal (GI) toxicity (CTCAE V5.0) was compared using Chi-square or Fisher’s exact test. Patient-reported bowel toxicity was evaluated using International Prostate Expanded Prostate Composite Index- Clinical Practice (EPIC-CP) and compared using linear mixed modeling. Results: 164 patients were eligible for analysis: 38 Ph-RS, 50 Ph+RS, 26 Pr-RS, & 50 Pr+RS. Median follow-up was 17.6 months. In men treated with protons, physician-reported acute G1-2 GI toxicity was significantly lower in men with versus without rectal spacer (6.12 vs 30.77%, Pr+RS vs Pr-RS, respectively; p=0.009) and there was a trend towards lower late G1-2 GI toxicity (8.51 vs 26.09%, Pr+RS vs Pr-RS, respectively; p=0.08). In men treated with photons, there were no significant differences in physician-reported acute or later GI toxicity with versus without rectal spacer. No significant differences in patient-reported outcomes were observed with versus without spacer in the proton or photon cohorts. Conclusions: Rectal spacer use was associated with a lower CTCAE grade 1-2 acute GI toxicity in men treated with protons, and this difference was not observed in men treated with photons. While this study is limited by low sample size, a relatively greater benefit of rectal spacer with proton vs. photon therapy was observed. Further prospective analyses in larger cohorts are ongoing to validate these hypothesis-generating findings.