{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:35:52Z","timestamp":1792157752640,"version":"4.4.0"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Urothelial carcinoma (UC) is characterized by high recurrence rates and the need for long-term surveillance. Cystoscopy remains the diagnostic gold standard but is invasive, costly, and burdensome for patients. Urine, as a tumor-proximal and non-invasive biospecimen, represents an attractive source for biomarkers enabling screening, diagnosis, risk stratification, and follow-up. Objective: This review summarizes current and emerging urine-based diagnostic approaches for UC, ranging from conventional cytology to advanced molecular technologies, and discusses their clinical utility, limitations, and future perspectives. Methods: A narrative review of the literature was conducted focusing on urine-based diagnostics for UC, including urinary cytology, FDA-approved and investigational protein and DNA\/RNA biomarkers, next-generation sequencing (NGS), cell-free DNA (cfDNA), exosomes, and microRNAs. Evidence from clinical validation studies, meta-analyses, and translational research was evaluated. Results: Urinary cytology remains highly specific for high-grade disease but has limited sensitivity for low-grade tumors. Protein- and DNA-based biomarkers have improved sensitivity but often lack sufficient specificity for standalone use. Recent advances in NGS-based assays enable comprehensive detection of tumor-specific genomic alterations in urinary cfDNA, offering high sensitivity for both initial diagnosis and disease monitoring. Exosomes and microRNAs represent promising biomarkers reflecting tumor biology, though standardization and large-scale validation are ongoing challenges. Overall, multimodal approaches combining cytology with molecular assays appear most promising for clinical implementation. Conclusions: Urine-based diagnostics are rapidly evolving toward integrated liquid biopsy platforms capable of transforming UC management. While several assays show strong potential to reduce reliance on cystoscopy, robust prospective validation, cost-effectiveness analyses, and clinical integration strategies are required before widespread adoption.<\/jats:p>","DOI":"10.3390\/jpm16030135","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T08:51:57Z","timestamp":1772441517000},"page":"135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Urine-Based Approaches for Screening, Diagnosis, and Surveillance of Urothelial Carcinoma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-1671","authenticated-orcid":false,"given":"Vladimir","family":"Bilim","sequence":"first","affiliation":[{"name":"Department of Urology, Kameda Daiichi Hospital, Niigata 950-0165, Japan"},{"name":"Department of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senji","family":"Hoshi","sequence":"additional","affiliation":[{"name":"Affiliated Long-Term Care Health Facility, Sendai South Hospital, Japan Community Healthcare Organization, Sendai 980-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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