Rectal Volume and Quality of Life in Prostate Cancer Patients Receiving Pediococcus-Based Probiotics and Radiation Therapy: A Prospective Randomized Trial

Abstract

Previous research identified Lactobacillus-based probiotic administration significantly reduced median and percent rectal volumes in prostate cancer (PC) patients undergoing daily radiation therapy (RT). However, Lactobacillus is sensitive to the acidic environment in the stomach. Pediococcus-based probiotics are resistant to pH as low as 1.5. We designed a prospective randomized trial to determine if administration of a Pediococcus-based probiotic therapy is feasible in patients undergoing prostate RT. An exploratory aim was to determine if probiotic therapy decreased rectal volumes throughout RT for PC compared to placebo.This was a single-institution prospective randomized study for men with PC undergoing prostate-only RT. Patients were randomized 1:1 to probiotic (2 gelatin capsules containing 4 × 109 colony-forming units of Pediococcus-based probiotics) or placebo. Administration of study agent was initiated 10 days prior to the start of daily RT. Quality of life (QOL) EPIC - Bowel Domain only surveys were completed at baseline, midway during RT, end of RT, and 1-month follow-up. Toxicities were recorded in accordance with CTCAE v5. Rectal volumes were contoured per the Radiation Therapy Oncology Group guidelines on the initial CT simulation, week 2, and week 6 using quality assurance CTs or cone-beam CTs, and compared using an independent samples Mann-Whitney U-test.Thirty patients were enrolled to the study. Two patients withdrew prior to initiating treatment, leaving 28 patients with evaluable data. Seven patients withdrew from the study for a completion rate of 75%. Of the patients that withdrew, 6 of 7 were on the placebo arm. In the placebo arm, one withdrew before starting the pills and five cited inconvenience as the reason for discontinuation. In the probiotic arm, one participant reported "increased blood pressure" which did not resolve with cessation; this was the only protocol-related toxicity. There were no differences in QOL in bowel function or bother scores between the two groups relative to each patient's baseline. The relative rectal volumes at week 2 (RV2) and 6 (RV6) were not significantly different between probiotic and control arms. RV2 averaged across all patients in each of the two trial arms was 9.9% larger in the probiotic arm compared with controls, RV2p/RV2c = 1.099 with 95% significance limits 0.82 and 1.47, P = 0.51. At 6 weeks, RV6p/RV6c = 0.868, 95% CI 0.654 to 1.152, P = 0.31.While feasible and with rare protocol-related toxicity, compliance with daily capsule administration during conventionally fractionated prostate RT proved difficult, with 25% of patients withdrawing before study completion. Within the limitations of this pilot study, Pediococcus-based probiotic administration did not significantly alter QOL metrics or rectal volumes.