Urinary biomarkers for cancer diagnosis and surveillance: From analytical promise to clinical utility

Urine is an attractive source of cancer biomarkers because it can be collected non-invasively and repeatedly, yet high diagnostic accuracy in early studies has rarely translated into routine care. This structured critical narrative review evaluates urinary proteins, nucleic acids, extracellular-vesicle cargo, and metabolites according to intended clinical use and evidence maturity rather than biomarker class alone. The review focuses on bladder and prostate cancers, while placing exploratory evidence in other malignancies in context. Evidence is appraised across analytical validity, external clinical validation, incremental value over contemporary diagnostic pathways, clinical utility, guideline and regulatory status, and implementation feasibility. Urinary tests show their clearest near-term value as adjuncts: in risk-adapted evaluation or surveillance for selected patients with bladder cancer and in pre-biopsy prostate cancer risk stratification after prostate-specific antigen testing, often integrated with magnetic resonance imaging and clinical risk factors. However, inconsistent pre-analytical procedures, spectrum and selection bias, limited prospective multicenter validation, absence of outcome-based utility studies, and uncertain cost-effectiveness continue to impede adoption. Professional guidelines therefore do not support indiscriminate replacement of cystoscopy or established prostate diagnostic pathways with urinary biomarkers. Multi-omics and artificial intelligence may improve performance, but require locked assays, transparent reporting, calibration, independent external validation, and workflow evaluation. Future progress depends less on discovering additional isolated markers than on validating context-specific tests that demonstrably improve clinical decisions, patient outcomes, and resource use.