Diagnostic Performance and Clinical Utility of the Uromonitor^® Molecular Urine Assay for Urothelial Carcinoma of the Bladder: A Systematic Review and Diagnostic Accuracy Meta-Analysis

Background: Urine cytology remains widely used for surveillance of non-muscle-invasive bladder cancer despite well-known limitations in sensitivity, especially for low-grade tumors. Uromonitor^®, a molecular assay detecting TERT promoter, FGFR3, and KRAS mutations in voided urine, has emerged as a promising adjunct. To evaluate its suitability for routine use, a consolidated assessment of diagnostic performance and a direct comparison with urine cytology are needed. Methods: We conducted a prospectively registered systematic review (PROSPERO CRD420251173244), synthesizing all available studies that evaluated Uromonitor^® for the detection of urothelial carcinoma of the bladder (UCB). Methodological quality was assessed using the QUADAS-2 framework, and certainty of evidence was evaluated following GRADE for diagnostic tests. Sensitivity was prespecified as the primary endpoint. Comparative datasets were identified, and random-effects meta-analyses were performed for sensitivity, specificity, accuracy, and predictive values (PVs). Results: Across eight cohorts evaluating Uromonitor^®, 832 of 3196 patients (26.0%) had histologically confirmed UCB. Aggregated sensitivity was 0.55 (95% CI 0.52–0.58). Specificity was 0.95 (0.94–0.96). Accuracy was 0.85 (0.83–0.86). PPV was 0.79 (0.76–0.82), and NPV was 0.86 (0.84–0.87). Across seven paired datasets, urine cytology demonstrated a sensitivity of 0.42, a specificity of 0.91, an accuracy of 0.78, a PPV of 0.64, and an NPV of 0.81. Pooled odds ratio for sensitivity was 3.16 (0.73–13.76), while diagnostic accuracy yielded 1.71 (1.01–2.90). Differences in specificity and NPV were not statistically significant, whereas the PPV favored Uromonitor^®, reaching statistical significance in pooled analyses. Conclusions: Uromonitor^® demonstrates higher sensitivity and improved accuracy compared with urine cytology, although current performance remains insufficient for stand-alone surveillance. The sensitivity estimate showed very low certainty due to pronounced heterogeneity, underscoring the need for careful interpretation. With advancing DNA recovery methods, incorporation of droplet digital PCR, and rigorous evaluations in prospective multicenter studies, Uromonitor^® may become an integral element of risk-adapted follow-up strategies.