Evaluating Molecular and Immune Biomarkers in Predicting Bladder Cancer Recurrence and Survival: A Systematic Review

This systematic review comprehensively evaluates current evidence on molecular and biochemical biomarkers for predicting recurrence and prognosis in bladder cancer. A literature search was conducted across PubMed, Scopus, and Web of Science databases up to September 2025, identifying 347 records. After rigorous screening and eligibility assessment, five studies met the inclusion criteria. The included research encompassed a range of biomarker types, including circulating tumor DNA (ctDNA), immune infiltration markers, methylation signatures, systemic inflammatory indices, and gene expression-based predictive models such as COXEN. Despite heterogeneity in study designs, methodologies, and endpoints, consistent findings indicated that integrated molecular profiling substantially improves the prediction of recurrence and disease progression beyond conventional clinicopathologic parameters. Immune and genomic biomarkers showed strong potential for early detection of relapse, while methylation and enzymatic markers provided additional prognostic stratification. Although most studies demonstrated a moderate risk of bias due to exploratory or non-randomized designs, the overall methodological quality was acceptable. The findings underscore the clinical utility of biomarker-guided surveillance and personalized management strategies in bladder cancer, while highlighting the need for large-scale validation and standardization of biomarker assays in future research.