Accurate, non-invasive detection of urothelial carcinoma (UC) remains an unmet clinical need. Urinary tumor DNA (utDNA) assays have recently emerged as promising tools, but their comparative diagnostic performance across assay types remains uncertain. We conducted a systematic review and network meta-analysis in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement. PubMed, Cochrane Library, Web of Science, Google Scholar, and Clinical Trials.gov were searched through January 2025. We included studies evaluating the diagnostic accuracy of utDNA for UC detection and surveillance. Data were pooled using a frequentist random-effects model to estimate sensitivity, specificity, diagnostic odds ratios, and area under the curve (AUC). A total of 37 studies comprising 7,388 patients were included. The pooled sensitivity and specificity of utDNA were 79% (95% confidence interval [CI], 73%-84%) and 86% (95% CI, 83%-89%), respectively. utDNA demonstrated over 4-fold higher sensitivity than urine cytology while maintaining comparable specificity. Analysis method significantly affected sensitivity, with next-generation sequencing (NGS)-based methods showing higher sensitivity (0.83) compared with methylation-based methods (0.75; P = 0.01). Urinary tumor DNA testing offers clinically meaningful accuracy and could reduce the need for invasive cystoscopy in UC diagnosis and surveillance. Implementation studies and cost-effectiveness analyses are warranted to support integration into clinical practice. Clinical Trial Registration PROSPERO CRD420251011665.
Urologic oncology. 2026 May 25 [Epub ahead of print]
Shugo Yajima, Naoki Imasato, Tadayoshi Hashimoto, Shin Kobayashi, Genichiro Ishii, Hitoshi Masuda
Department of Urology, National Cancer Centre Hospital East, Chiba, Japan; Perioperative Treatment Development Promotion Office, National Cancer Center Hospital East, Chiba, Japan. Electronic address: ., Department of Urology, National Cancer Centre Hospital East, Chiba, Japan., Perioperative Treatment Development Promotion Office, National Cancer Center Hospital East, Chiba, Japan., Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan.