Roles for epigenetic and other biomarkers in upper tract urothelial carcinoma diagnosis and surveillance

Abstract

Upper tract urothelial carcinoma (UTUC) is a rare but aggressive malignancy with increasing incidence, often diagnosed at advanced stages due to the limitations of current diagnostic tools. Conventional methods such as urinary cytology, imaging, and ureteroscopy have important drawbacks, including low sensitivity, high costs, and procedural invasiveness. As a result, there is a growing need for non-invasive, highly accurate diagnostic approaches.

Epigenetic biomarkers, particularly DNA methylation-based assays, have emerged as promising alternatives for UTUC detection and surveillance. Among these, Bladder EpiCheck® (BE) has shown remarkable sensitivity and specificity, particularly for high-grade tumors, making it a valuable adjunct to standard diagnostic techniques. By analyzing tumor-specific methylation patterns in urine samples, BE offers a practical and non-invasive solution that could improve early detection, reduce the need for ureteroscopy, and enhance risk stratification. Several studies have demonstrated its superior diagnostic accuracy, with sensitivity reaching 97.4 % and specificity up to 100 % for high-grade UTUC.

Despite these advantages, challenges remain regarding the standardization of testing protocols, validation in larger patient cohorts, and evaluation of cost-effectiveness. Moreover, the role of DNA methylation biomarkers in guiding clinical decisions and predicting disease progression requires further investigation. This review explores the current state of UTUC diagnosis, compares BE with conventional and emerging biomarkers, and discusses its clinical applications, limitations, and future perspectives. The integration of molecular biomarkers like BE into clinical practice has the potential to revolutionize UTUC diagnosis, improving patient outcomes through more precise, non-invasive detection strategies.