Background/Objectives: Prostate cancer is the most frequent cancer in men, for which Radiotherapy (RT) is used as a radical or post-surgical treatment. Actinic proctitis is one of the most disabling side effects of RT. Intestinal microbiome studies have highlighted the importance of short-chain fatty acids, in particular butyric acid, for their beneficial effects over intestinal epithelial cells. The aim of this prospective study is to evaluate if treatment with micro-encapsulated sodium butyrate (MESB) can reduce the incidence of actinic proctitis during RT in prostate cancer patients. Methods: In total, 122 consecutive patients with prostate cancer treated in Radiotherapy Unit, Centro di Riferimento Oncologico, IRCCS Aviano, were enrolled. Patients received MESB (3 tablets/day) from one week before until four weeks after RT. They completed a diary, tracking daily bowel movements, rectal bleeding, abdominal pain, and perceived health status before, at the end, and one month after RT. Results: Although an improvement in symptoms was observed, when comparing interpatient data before RT vs. one month after the end of RT, statistically significant differences emerged only regarding abdominal pain (94.2% vs. 81.6% vs. 81.6%) (McNemar’s test p < 0.002). Conclusions: MESB appears effective in reducing radiation-induced bowel toxicity during RT, minimizing stool changes, incontinence, and abdominal pain. Although patients’ health perception declined at RT completion, it improved after one month, suggesting MESB may support clinical recovery post-treatment.
