Urinary Extracellular Vesicle-Associated Non-Coding RNAs in NMIBC Surveillance: Intended Use and Evidence Maturity

This structured narrative review evaluates urinary extracellular vesicle-associated non-coding RNAs (uEV-ncRNAs) as biomarkers for non-muscle-invasive bladder cancer (NMIBC). Using the 2026 EAU and NCCN guidance as the clinical benchmark, we distinguish cross-sectional cancer detection from posttreatment surveillance, progression-risk assessment and BCG-response applications. Searches of PubMed/MEDLINE and Web of Science Core Collection covered database inception through 17 July 2026, with targeted guideline and bibliographic checks during revision. Most clinical studies used case–control designs and compared prevalent bladder cancer with healthy or benign controls; few aligned sampling, reference standards and endpoints with serial NMIBC surveillance. We therefore classify evidence by intended-use applicability and, separately, by validation maturity, distinguishing internal validation, independent validation within the same clinical environment and genuinely external validation. A recent NMIBC-specific three-lncRNA study used training, validation and blinded validation samples, but remained a single-environment diagnostic study rather than external surveillance validation. Across studies, heterogeneity in urine collection, EV enrichment, RNA normalization, control selection and model development limits transportability. Current evidence supports uEV-ncRNAs as investigational adjuncts. Locked assays, risk-specific surveillance cohorts, incremental comparison with cytology and established urine tests, external multicenter validation and prospective decision-impact trials are required before cystoscopy can be reduced safely.