Urinary biomarkers in multicentric studies: Shaping the future of bladder cancer diagnosis and follow-up.

Background and Objective: Bladder cancer (BC), a prevalent malignancy, poses significant diagnostic and surveillance challenges due to its high recurrence rates and reliance on cystoscopy, an invasive procedure for diagnosis and monitoring. While urine-based genomic and proteomic biomarkers offer promising non-invasive alternatives, their clinical implementation remains limited. This review synthesizes evidence from multicentric studies on urinary biomarkers for BC and evaluates their potential in reducing unnecessary invasive cystoscopies. Methods: A comprehensive review of literature was conducted searching for multicentric studies on urine-based genomic and proteomic biomarkers for BC detection and/or surveillance. MEDLINE/Pubmed, Embase and Scopus databases and BJUI, UroToday and European Urology Oncology registries were searched using National Library of Medicine Medical Subject Headings (MeSH) terms. Emphasis was placed on the comparative performance of diagnostic platforms across different research and clinical settings. Key Findings and Limitations: The literature search yielded 51 reports that were included for analysis. Multicentre studies enhance the generalizability of findings by addressing inter-laboratory variability and population diversity. This review underscores the importance of standardization, comparative performance analyses that these studies provide, and the potential for cost-effective non-invasive diagnostic tools. However, despite FDA approvals, no biomarker has replaced cystoscopy in clinical settings due to an inconsistent and insufficient combination of sensitivity, specificity and cost-effectiveness parameters. The performance of AssureMDX and Enhanced CxBladder tests showed the most promise, but further large-scale, standardized validation is still necessary. Conclusions and Clinical Implications: Urine-based biomarkers have the potential to improve early BC detection and surveillance while reducing reliance on invasive procedures and costs related to the disease. Future efforts should prioritize cost-effective, large-scale multicentric studies to facilitate the adoption of these biomarkers into routine practice.