Urinary Tumor DNA-based Liquid Biopsy in Bladder Cancer Management: A Systematic Review

Background and objective: Urinary tumor DNA (utDNA) has emerged as a promising biomarker in the care, diagnosis, early detection, recurrence monitoring, and prognosis of bladder cancer (BCa). Its noninvasive nature, ease of access, and cost effectiveness make it an attractive option for both patients and health care providers. This review describes the current state of utDNA as a marker of BCa. Methods: Articles published between 2015 and 2025 on current utDNA-based techniques in BCa were identified and analyzed for relevance and insight into utDNA research and usage. Key findings and limitations: Recent investigations underscore the noninvasiveness and superior tumor detection capabilities of utDNA, particularly in the detection of minimal residual disease. Moreover, utDNA provides actionable information, such as tumor grade and staging information, to support precise treatment decisions, including targeted immunotherapy regimens and bladder preservation strategies. Although utDNA has shown promising results in small studies, larger studies must be performed before it can be considered as a standard procedure in clinical practice. Conclusions and clinical implications: Urinary tumor DNA has demonstrated great potential to improve on most, if not all, stages of detection, treatment, and monitoring of BCa. By preserving the low cost and noninvasiveness of urine cytology, and by replacing its suboptimal accuracy with a precision rivaling and often exceeding cystoscopy and circulating tumor DNA-based methods, utDNA offers patients a more comfortable, repeatable, and accurate way of detecting BCa. With increased sensitivity and accuracy, everything from low-grade tumors to the earliest signs of recurrence can be detected more effectively, optimizing patient treatment courses and improving outcomes.