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.