Digital Uromonitor® outperforms quantitative polymerase chain reaction Uromonitor and cytology for non‐muscle‐invasive bladder cancer surveillance: results from the ‘External Validation of Uromonitor as a Biomarker for Optimization of NMIBC Managemen

OBJECTIVE: To compare the performance of a new digital Uromonitor® (dUM; U-Monitor, Porto, Portugal) against the previous quantitative polymerase chain reaction (qPCR) version and cytology in the follow-up of non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: This retrospective (post hoc) molecular analysis of a prospectively collected multicentre cohort re-analysed stored urine DNA samples from the 'External Validation of Uromonitor as a Biomarker for Optimization of NMIBC Management by the Club Urológico Español de Tratamiento Oncológgico Group' (EVALUATION-CUETO) study (ClinicalTrials.gov identifier: NCT05864599). Samples, previously tested with Uromonitor-version 2, were analysed using dUM (QX200™ Droplet Digital PCR System) for TERT and FGFR3 hotspot mutations. Performance metrics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], area under the curve [AUC]) for detecting recurrence were calculated against cystoscopy/histology and compared to qPCR and cytology. The study received approval from the Ethical Committee at the University Hospital of Vall d'Hebron (Barcelona). RESULTS: Analysis of 271 samples revealed dUM had superior sensitivity to qPCR (72% vs 36%) and cytology (72% vs 34%), while preserving high specificity (88%) and NPV (93%). The AUC for dUM was 0.80 vs 0.66 for qPCR. Performance was consistent across tumour grades and risk groups. Crucially, combining a positive/suspicious cystoscopy with a positive dUM result significantly increased the PPV to 94% (from 79% for cystoscopy alone). CONCLUSION: The dUM significantly outperformed its qPCR predecessor and cytology in sensitivity for detecting NMIBC recurrence in a real-world setting, without compromising specificity. Its high NPV supports its potential for reducing unnecessary cystoscopies. Furthermore, its combination with cystoscopy drastically increased the PPV, suggesting a role as an adjunctive tool to improve diagnostic confidence and potentially reduce unnecessary transurethral resections of bladder tumour, pending favourable cost-effectiveness.