Urinary tumor DNA as a biomarker of pathologic response and molecular residual disease in muscle-invasive bladder cancer: A systematic review.

e15055 Background: Despite advances in multimodal therapy, recurrence after curative-intent treatment for muscle-invasive bladder cancer (MIBC) remains common. Urine-derived tumor DNA (utDNA)represents a non-invasive biomarker that may refine risk stratification, predict treatmentresponse, and detect molecular residual disease (MRD). We systematically reviewed the clinicalutility of utDNA in non-metastatic MIBC. Methods: Following PRISMA guidelines and a pre-registered protocol (PROSPERO: CRD420251147550),PubMed, Embase, Scopus, and clinicaltrials.gov were searched through October 2025 withoutlanguage restriction. Eligible studies enrolled adults with non-metastatic MIBC undergoingdiagnostic evaluation, radical cystectomy (RC), or bladder-preserving therapy, evaluatingutDNA. Screening, data extraction, and quality appraisal were performed independently induplicate using the Newcastle–Ottawa Scale (NOS), QUADAS-2, and GRADE frameworks. Results: Of 245 screened records, eight studies comprising 306 patients met inclusion criteria. Overallmethodological quality was moderate, with all studies observational and heterogeneous inassay platforms, urine fractions analyzed, timing of sample collection, and outcome definitions.Urinary tumor DNA was consistently detectable across cohorts, with detection rates generallyhigher than matched plasma ctDNA. Across studies, utDNA positivity—particularly afterneoadjuvant therapy or prior to definitive treatment—was associated with residual pathologicdisease, absence of pathologic complete response, and lower rates of pathologic downstaging.Longitudinal analyses further demonstrated that persistence or rising utDNA levels correlatedwith worse oncologic outcomes, while declining utDNA burden paralleled treatment response.Despite heterogeneity and limited sample sizes, the direction of association between utDNApositivity and adverse pathologic or prognostic outcomes was consistent across studies. Conclusions: Urinary tumor DNA demonstrates feasibility and promising diagnostic,predictive, and prognostic value in MIBC. Standardization of assay platforms and multicentervalidation are needed before integration into MRD-guided clinical decision-making.