Immunological and inflammatory biomarkers of localized and locally advanced prostate cancer treated with radiotherapy.

Radiotherapy r5emains a cornerstone of treatment for localized and locally advanced prostate cancer, yet substantial heterogeneity persists in oncological outcomes and treatment-related toxicity. Increasing evidence suggests that systemic inflammation, immune microenvironment characteristics, and tumor-specific molecular features contribute to these variations and may provide clinically relevant biomarkers. This narrative review summarizes current evidence regarding immunological and inflammatory biomarkers in prostate cancer treated with radiotherapy, focusing on their biological rationale, prognostic significance, predictive potential, and clinical applicability. Circulating biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein, fibrinogen, and cytokines such as IL-6 and TGF-β1, have been associated with oncological outcomes and toxicity in several studies. However, their interpretation remains limited by biological nonspecificity, methodological heterogeneity, variable cutoff definitions, and lack of prospective validation. Within the tumor microenvironment, immune cell populations, including CD8+ tumor-infiltrating lymphocytes, regulatory T cells, CD163+ macrophages, and immune checkpoint molecules, provide insights into tumor-immune interactions and radiotherapy-induced immune modulation. Emerging biomarkers such as extracellular vesicles, circulating tumor DNA, circulating tumor cells, and microRNAs offer promising opportunities for disease monitoring and treatment adaptation, although most evidence remains preliminary, particularly in localized disease. In contrast, genomic classifiers such as Decipher, Prolaris, and OncotypeDX currently represent the most clinically mature biomarker platforms for risk stratification and treatment decision support. Although several biomarkers demonstrate biological plausibility and prognostic value, few have sufficient clinical validation to guide routine radiotherapy decision-making. Future multicenter prospective studies, standardized biomarker assessment protocols, and integrated approaches combining clinical, imaging, molecular, and immune data are required to enable clinically actionable precision radiotherapy strategies.