Molecular Clearance After TURBT: A Systematic Review of Postoperative Urinary Nucleic-Acid Assays for Detecting Residual Disease and Guiding Repeat TURBT in High-Risk Non–Muscle-Invasive Bladder Cancer

Background/Objectives: Repeat transurethral resection of bladder tumor (TURBT) remains important in selected high-risk non-muscle-invasive bladder cancer (NMIBC) because residual tumor may persist after initial resection, yet some patients may undergo an ultimately tumor-negative procedure. Postoperative urinary molecular testing may provide a noninvasive approach to identify residual disease before repeat TURBT. This review evaluated the diagnostic performance and potential triage value of postoperative urinary nucleic-acid assays for detecting histologically confirmed residual tumor before repeat TURBT in patients with high-risk NMIBC. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched. Eligible studies included adults with high-risk NMIBC undergoing initial TURBT, postoperative urinary nucleic-acid testing before repeat TURBT, and histopathological residual-disease assessment. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies, version 2 (QUADAS-2). Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) for diagnostic test accuracy. Findings were synthesized narratively. Results: Of 3231 records, four studies met the eligibility criteria. Performance varied across assays. UroAmp Prognosis achieved 97% sensitivity and 89% negative predictive value (NPV); UroAmp minimal residual disease (MRD) achieved 72% sensitivity, 80% specificity, and 57% NPV. utLIFE achieved 80.7% sensitivity, 96.2% specificity, and 90.1% NPV. The H4 Clustered Histone 6 (H4C6)/Twist Family bHLH Transcription Factor 1 (TWIST1) methylation panel achieved 65.2% sensitivity, 87.5% specificity, and a calculated NPV of 77.8%. OncoUrine achieved an NPV of approximately 82% in the high-risk subgroup. Certainty was very low for UroAmp Prognosis, UroAmp MRD, the H4C6/TWIST1 panel, and utLIFE, and low for OncoUrine in the high-risk subgroup. No included study evaluated omission of repeat TURBT based on a negative molecular result. Conclusions: Postoperative urinary molecular assays remain promising investigational tools, but the available evidence is of low to very low certainty and does not establish that repeat TURBT can safely be omitted after a negative result. Prospective external validation and management-impact studies are required before routine clinical use for this purpose.