Predictive Factors for Acute and Late Genitourinary and Gastrointestinal Toxicity Following Modern Radiotherapy for Prostate Cancer: A Narrative Review of Clinical, Dosimetric, Immunological, and Genetic Determinants

Abstract

Background: Despite advances in prostate cancer (PC) radiotherapy, including intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiotherapy (SBRT), genitourinary (GU) and gastrointestinal (GI) toxicities remain important complications. Identifying reliable predictors is essential for personalized treatment. Objective: The aim of this study was to summarize current evidence on clinical, dosimetric, immunological, and genetic predictors of acute and late GU and GI toxicities after PC radiotherapy. Materials and Methods: A structured literature review of studies published between 2000 and 2026 was conducted using PubMed, Scopus, and Europe PMC. Eligible studies included clinical investigations, randomized controlled trials, meta-analyses, and reviews assessing toxicity according to RTOG and/or CTCAE criteria. Results: GU toxicity was associated with pretreatment International Prostate Symptom Score (IPSS), large prostate volume, prior TURP, smoking, alpha-blocker use, and bladder/urethral dose. GI toxicity correlated with rectal dose–volume parameters, anorectal irradiation, anticoagulant therapy, and cardiovascular comorbidities. Acute grade ≥ 2 toxicity predicts late toxicity. Preliminary data from small single-center cohorts associate elevated IL-6, TGF-β1, TNF-α, and systemic immune-inflammation index with higher toxicity risk, and higher lymphocyte counts with lower risk; these findings require prospective validation. The PROSTOX radiogenomic signature is promising for the prediction of late GU toxicity but still requires independent external validation in larger, ethnically diverse cohorts with longer follow-up, and is not currently suitable for routine clinical decision-making. Conclusions: GU and GI toxicities have distinct predictive profiles. Integrating clinical, dosimetric, immunological, and genetic factors may improve personalized radiotherapy, although prospective multicenter validation remains necessary.