Emerging biomarkers in bladder cancer: Translating molecular advances into precision oncology

Bladder cancer (BC) is a heterogeneous malignancy of the urinary tract with significant clinical challenges in diagnosis, prognosis, and treatment. The rise of precision medicine offers new hope for more personalized management, driven by biomarker discovery and molecular profiling. This review explores the landscape of emerging biomarkers in BC, discussing in detail diagnostic, prognostic, and predictive implications in the present and further scenarios for improving clinical management of BC patients. An in-depth analysis of the current literature was conducted, with attention to genomic (e.g., FGFR3, TP53, ERBB2), epigenetic (DNA methylation, non-coding RNAs), transcriptomic (molecular subtypes and RNA signatures), proteomic, and immunological biomarkers (PD-L1, TMB, MSI). Multiple biomarkers are already influencing clinical decision-making, such as FGFR-targeted therapy in patients with FGFR3 mutations and immune checkpoint inhibitors (ICI) in PD-L1-expressing tumors. Molecular subtyping enables stratification of muscular-invasive BC into luminal, basal, and neuroendocrine-like subtypes with distinct therapeutic implications. Urinary and blood-based biomarkers show promise for non-invasive monitoring, though challenges remain in clinical validation. Biomarkers are central to the transition from empirical to personalized care in BC. While several markers are already clinically actionable, future implementation will depend on overcoming technical, regulatory, and economic barriers. Integrating genomic, transcriptomic, and immunological data, supported by artificial intelligence and digital pathology, will be key to unlocking the full potential of precision medicine in urothelial carcinoma.