Radiation therapy as a potential approach to enhancing the efficacy of targeted radionuclide therapy in metastatic castration-resistant prostate cancer

The combined use of external beam radiotherapy (EBRT) and targeted radionuclide therapy (tRNT) is considered a promising strategy to overcome resistance and enhance treatment efficacy in metastatic castration- resistant prostate cancer (mCRPC). Objective. The aim of the study is to analyze and synthesize current preclinical and clinical data justifying the potential synergism of combining EBRT (including photon and proton therapy) with PSMA-targeted tRNT Materials and methods. This review was performed in accordance with the key principles of the PRISMA guideline to ensure transparency and reproducibility of the literature search and selection process. Search for relevant publications was carried out in electronic databases PubMed/MEDLINE, Scopus and eLibrary. ru and covered the period from January 2000 to May 2024. Results. Based on a comprehensive database search (PRISMA approach), the authors analyzed radiobiological mechanisms of interaction, including radiation-induced modulation of PSMA expression, the principle of spatial cooperation, and cumulative dosimetry issues. Furthermore, successful experiences with combination regimens in other malignancies (hepatocellular carcinoma, lymphomas, and neuroendocrine tumors) were reviewed in detail, serving as a conceptual framework for developing prostate cancer protocols. Conclusion. Despite the limited number of direct clinical trials in prostate cancer, the accumulated preclinical and indirect clinical evidence strongly demonstrates the necessity and rationale for conducting controlled pilot Phase I/II trials to evaluate safety, determine optimal regimens and dosimetry models, and identify predictors of response to the combination therapy.