Meta-analysis finds blood biomarkers predict outcomes in anal cancer but need validation

BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence. Prognosis is based on clinical factors, which may not fully capture tumour biology or host immune response. Blood-based biomarkers are inexpensive, accessible, and repeatable, making them attractive prognostic tools. METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines (PROSPERO CRD42024547045). PubMed, EMBASE, and Web of Science were searched to July 2024 for studies reporting blood-based biomarkers in ASCC treated with curative chemoradiotherapy (CRT). Eligible studies reported overall survival (OS), disease-free survival (DFS), or locoregional control (LRC). Hazard ratios (HRs) were pooled using random-effects models when ≥ 3 studies were available per biomarker-outcome pair. Risk of bias was assessed with ROBINS-E. RESULTS: Twenty-six studies (n = 3589) were included, of which 13 contributed to meta-analysis. For OS elevated neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), white cell count (WCC), and low haemoglobin (Hb) all trended toward poorer outcomes, though none reached significance. For DFS, low Hb was significantly associated with inferior survival (HR 2.69, 95 % CI 1.46-4.97), and elevated NLR predicted worse DFS (HR 1.13, 95 % CI 1.01-1.25). Additional biomarkers were described narratively, though evidence was limited. CONCLUSIONS: Hb and NLR show prognostic value for DFS in ASCC, while several other blood-based markers demonstrate consistent trends for OS. However, heterogeneity and small study numbers limit clinical application. These biomarkers are not yet as robust as clinicopathologic factors and prospective validation is required.