Bladder Epicheck Test: A Novel Tool to Support Urothelial Carcinoma Diagnosis in Urine Samples

Abstract

Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.

Keywords: bladder carcinoma; methylation; tumoral recurrence; urinary biomarkers.

Figure 1

Correlation between the histological recurrences of high-grade urothelial carcinoma and the EpiScore values. On the x-axis and in table: NT and T on the x-axis and in the correlated table indicate no tumor and tumor, respectively. Reprinted/Adapted with permission from ref. [26]. Copyright year: 2022; Copyright Owner’s Name: Cancer Cytopathology.

Figure 2

The ROC curves of Bladder EpiCheck (A) and cytology (B). In (A) the area under the curve (AUC) for the diagnostic accuracy was 0.995 (p < 0.001; 95% CI (confidence interval) from 0.870 to 0.988; Youden index J = 0.8756; sensitivity 92%; specificity 95,5%), while in (B) it was 0.855 (p < 0.001; 95% CI from 0.751 to 0.928; Youden index J = 0.6699; sensitivity 69.7%; specificity 97.3%). Reprinted/Adapted with permission from ref. [34]. Copyright year: 2022. Copyright Owner’s Name: Urologic Oncology: Seminars and Original Investigations.