Bladder Cancer Biomarkers: Recent Advances in Early Detection, Treatment Prediction, and Prognosis

Bladder cancer (BC) is a prevalent malignancy characterized by a high recurrence rate and the necessity for long-term surveillance demands, creating a need for accurate yet practical tools for early detection and monitoring. While current standards including cystoscopy, urinary cytology, and imaging remain indispensable, their clinical utility is constrained by invasiveness, suboptimal sensitivity for selected lesions or low-grade lesions, inter-observer variability, and cumulative costs. Currently, biomarker research has expanded from single protein assays to multi-analyte strategies encompassing DNA, RNA, proteins, extracellular vesicle-associated cargo, and metabolomics signatures. This review synthesizes recent advances in diagnostic, surveillance, prognostic, and treatment-predictive biomarkers, with emphasis on assay principles, analytical platforms and reported performance where available. Furthermore, we delineate critical barriers to translation, including limited prospective multicenter validation, heterogeneous pre-analytical workflows, inconsistent thresholds, and the persistent trade-off between sensitivity and specificity in real-world benign urologic conditions. Ultimately, while emerging biomarkers and multi-omics panels hold transformative potential as non-invasive adjuncts in risk-adapted clinical pathways, their routine adoption is contingent upon rigorous clinical integration and standardized validation.