Urine-Based Biomarkers in the Diagnosis of Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-Analysis

Background: Upper tract urothelial carcinoma (UTUC) is a rare malignancy with a poor prognosis. Current diagnostic methods such as ureteroscopic biopsy and imaging techniques are invasive, costly, or have low sensitivity. Urine-based biomarkers represent a promising non-invasive alternative. Objective: To systematically review and meta-analyze the diagnostic accuracy of various urine-based biomarkers for UTUC and provide a head-to-head comparison. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Embase, Cochrane, and Web of Science from January 2000 to October 2025. Studies meeting PICOS criteria were included. Diagnostic performance metrics including sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were extracted. Data were synthesized using the MIDAS module in StataMP 18.0. Results: Seventeen studies involving 2734 patients were included. The overall pooled sensitivity was 0.86, specificity 0.94, diagnostic odds ratio 93, and AUC 0.94. DNA methylation assays showed balanced performance (SEN = 0.89, SPE = 0.92), gene mutation assays had the highest specificity (SPE = 0.97), RNA assays had the highest sensitivity (SEN = 0.97) but low specificity (SPE = 0.25). Significant heterogeneity was observed, but no notable publication bias was detected. Conclusions: Urine-based biomarkers demonstrate high diagnostic performance for UTUC, particularly DNA methylation assays. Future prospective studies are warranted to validate their clinical utility.