Selected Blood-Accessible Biomarkers in Prostate Cancer Radiotherapy: A PRISMA-ScR Timing-Window Framework Beyond PSA

Background: Blood-accessible biomarkers may support future personalization of prostate cancer radiotherapy, but their interpretation depends on sampling timing relative to radiotherapy, androgen deprivation therapy, and post-treatment recovery. We mapped clinical evidence for selected biomarker domains beyond prostate-specific antigen: γ-H2AX/DNA damage response, IL-6/inflammatory mediators, testosterone/endocrine recovery and a prespecified galectin-1/3 immune-stromal domain evaluated as a potential evidence gap. Methods: We conducted a PRISMA-ScR scoping review of PubMed, Scopus, and Web of Science searched on 7 January 2026. Eligible original human studies evaluated soluble serum/plasma analytes or peripheral blood cell-based assays in prostate RT pathways. Data were charted by biomarker domain, treatment context, RT modality/fractionation, assay reporting, sampling schedule, and endpoint linkage. Results: Of 3499 records, 45 studies were included. No eligible study reported repeated circulating galectin-1/3 kinetics anchored to prostate radiotherapy, identifying a distinct clinical evidence gap. The remaining evidence was dominated by testosterone studies (n = 28), followed by IL-6/inflammatory mediators (n = 12) and γ-H2AX/DDR (n = 5). Testosterone studies were mapped as separate RT-only endocrine kinetics and ADT-anchored recovery streams. IL-6 studies mainly used during-RT or early post-RT sampling and linked trajectories to acute toxicity, fatigue, symptoms or inflammatory phenotypes; no included study directly validated serial IL-6/inflammatory trajectories against biochemical control, metastasis-free survival, or overall survival. γ-H2AX studies were characterized by ultra-acute, fraction-anchored sampling. Across domains, baseline definition and sampling timing limited interpretability more than assay platform alone. Conclusions: Evidence maturity was unequal across the selected domains. Testosterone provided the comparatively more developed longitudinal clinical literature, whereas IL-6/inflammatory mediators remained exploratory and were linked mainly to acute toxicity, fatigue, symptoms, and inflammatory phenotypes. γ-H2AX remained predominantly a translational and biodosimetry-oriented marker, while galectin-1/3 represented a hypothesis-generating clinical evidence gap. None of these biomarkers currently supports routine biomarker-guided prostate RT personalization. Future biomarker-embedded studies may benefit from domain-specific sampling considerations, explicit RT/systemic-therapy context stratification, standardized assay reporting, and clinically relevant endpoints.