ESTRO 2025 - Abstract Book

S1931

Clinical - Urology

ESTRO 2025

Purpose/Objective: Intestinal side effects after radiation therapy (RT) reduce quality of life (QoL) and limit treatment regimens of abdominopelvic tumors.[1] The pathogenesis underlying these side effects and the varying severity of the symptoms are still insufficiently understood. Preclinical and few larger clinical studies suggest a connection to the gut microbiome, yet the mechanisms causing these correlations remain elusive.[2-4] Our study aims to detect changes in the microbial composition of patients with recurrent prostate cancer undergoing RT and to correlate alterations with radiogenic side effects. Material/Methods: We designed an exploratory study to longitudinally examine patients with recurrent or incompletely resected (R1) prostate cancer receiving RT. Radiogenic side effects were analyzed using clinician-reported outcomes based on CTCAE v5.0. Stool samples were collected at two time points prior to RT, weekly during RT, and at follow-up (FU) 6 weeks after RT. Samples from an initial cohort (n=12) were purified, PCR amplified, and 16SrRNA-amplicons were sequenced. The sequencing data was processed and analyzed with Qiime2 and R. Patients were divided into 2 toxicity groups based on diarrhea development and compared by pooling all timepoints: high side effect group, defined as having a CTCAE score of ≥ 2 at any time point or ≥ 1 persisting at first FU; low side effect group, defined as having a CTCAE score of ≤ 1 during RT and 0 at first FU. Results: Alpha diversity did not differ significantly between toxicity groups. Principal Coordinates Analysis identified a significantly different community composition between toxicity groups. Taxonomic analysis uncovered several phyla differing between toxicity groups, with Bacteroidetes, Euryarchaeota and Verrucomicrobia being more abundant in the high toxicity group, while Actinobacteria were more prevalent in the low toxicity group. Linear Discriminant Analysis Effect Size was used to identify differentially abundant phyla between toxicity groups. A comparison of the relative abundances of these phyla revealed significant differences of Euryarchaeota, Verrucomicrobia and Actinobacteria between the toxicity groups. Conclusion: We identified Verrucomicrobia, Euryarchaeota, and Actinobacteria as potential factors that may explain the varying severities of intestinal side effects after pelvic RT. Further analyses are needed to explore their biomarker potential for predicting the development of these intestinal side effects. References: 1. Andreyev, H.J., et al., Defining pelvic-radiation disease for the survivorship era. Lancet Oncol, 2010. 2. Ferreira, M.R., et al., Microbiota and radiation-induced bowel toxicity: lessons from inflammatory bowel disease for the radiation oncologist. Lancet Oncol, 2014. 3. Wang, A., et al., Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS One, 2015. 4. Reis Ferreira, M., et al., Microbiota and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy. Clin Cancer Res, 2019. Keywords: prostate cancer, microbiome, side-effects