Real‐world performance of Uromonitor® in urothelial bladder cancer detection: a multicentric trial

Objectives To compare Uromonitor® (U‐Monitor Lda, Porto, Portugal), a multitarget DNA assay that detects mutated proto‐oncogenes (telomerase reverse transcriptase [ TERT ], fibroblast growth factor receptor 3 [ FGFR‐3 ], Kirsten rat sarcoma viral oncogene homologue [ KRAS ]), with urine cytology in the urine‐based diagnosis of urothelial carcinoma of the bladder (UCB) within a multicentre real‐world setting. Patients and Methods This multicentre, prospective, double‐blind study was conducted across four German urological centres from 2019 to 2024. We evaluated the diagnostic performance of Uromonitor compared to urine cytology in a cohort of patients with UCB and in healthy controls within a real‐world setting. Sensitivity, specificity, positive‐predictive value (PPV), negative‐predictive value (NPV), and accuracy of the tests were measured, in addition to multivariate analyses to assess the ability of individual proto‐oncogene mutations in detecting UCB. The biometric sample size was designed to achieve a 10% difference in sensitivity. Results Patients with UCB comprised 63.7% (339/532) of the study group. Uromonitor showed a sensitivity, specificity, PPV, NPV, accuracy, and an area‐under‐the‐curve of 49.3%, 93.3%, 92.8%, 51.1%, 65.2%, and 0.713%, respectively. These metrics did not demonstrate statistical superiority over urine cytology in terms of sensitivity (44.6%; P = 0.316). Moreover, the comparison of additional test parameters, as well as the comparison within various sensitivity analyses, yielded no significant disparity between the two urinary tests. Multivariate logistic regression underscored the significant predictive value of a positive Uromonitor for detecting UCB (odds ratio [OR] 9.03; P < 0.001). Furthermore, mutations in TERT and FGFR‐3 were independently associated with high odds of UCB detection (OR 13.30 and 7.04, respectively), while KRAS mutations did not exhibit predictive capability. Conclusion Despite its innovative approach, Uromonitor fell short of confirming the superior results anticipated from previous studies in this real‐world setting. The search for an optimal urine‐based biomarker for detecting and monitoring UCB remains ongoing. Results from this study highlight the complexity of developing non‐invasive diagnostic tools and emphasise the importance of continued research efforts to refine these technologies.