Diagnostic accuracy, clinical utility and influence on decision‐making of a methylation urine biomarker test in the surveillance of non‐muscle‐invasive bladder cancer

Abstract

ObjectivesTo investigate prospectively the clinical utility and influence on decision-making of Bladder EpiCheck TM , a non-invasive urine test, in the surveillance of non-muscle-invasive bladder cancer (NMIBC). Materials and MethodsUrine samples from 440 patients undergoing surveillance for NMIBC were prospectively collected at five centres and evaluated using the Bladder EpiCheck test (NCT02647112). A multivariable nomogram and decision-curve analysis (DCA) were used to evaluate the impact of Bladder EpiCheck on decision-making when used in routine clinical practice. The test was designed to exclude recurrent disease. ResultsData from 357 patients were available for analysis. The test had a specificity of 88% (95% confidence interval [CI] 84-91), a negative predictive value (NPV) of 94.4% (95% CI 91-97) for the detection of any cancer and an NPV of 99.3% for the detection of high-grade cancer. In multivariable analysis, positive Bladder EpiCheck results were independently associated with any and high-grade disease recurrence (odds ratio [OR] 18.1, 95% CI 8.7-40.2; P < 0.001 and OR 78.3, 95% CI 19.2-547; P < 0.001). The addition of Bladder EpiCheck to standard variables improved its predictive ability for any and high-grade disease recurrence by a difference of 16% and 22%, respectively (area under the curve 85.9% and 96.1% for any and high-grade cancer, respectively). DCA showed an improvement in the net benefit relative to cystoscopy over a large threshold of probability, resulting in a significant reduction in unnecessary investigations. These results were similar in subgroups assessing the impact of specific clinical features. ConclusionsBladder EpiCheck is a robust high-performing diagnostic test in patients with NMIBC undergoing surveillance that can potentially reduce the number of unnecessary investigations.

Diagnostic predictive value of the Bladder EpiCheck test in the follow‐up of patients with non–muscle‐invasive bladder cancer

“…The high NPV reported by previous studies could not be reached in our study (97%, 95.1%, and 94.4% vs 82.9%, respectively). The PPV in our study was superior to that reported by Witjes et al (68.2% vs 48.8%) but was not reported by Wassermann et al and thus cannot yet be discussed.…”

“…The specificity reported by Wasserstrom et al was 83%, and that in the studies by Witjes et al and D'Andrea et al was 88%, whereas the specificity in our study was 86.3%. However, the test could not reach the excellent specificity of cytology (98%) but nonetheless performed in an excellent way.…”

“…There are 2 recent studies. The study by Witjes et al included 440 patients and showed a drop‐out rate of 8.4%, an overall sensitivity of 68.2%, and a specificity of 88%; and the other study, by D'Andrea et al, also included 440 patients and showed an overall sensitivity of 67.3% and a specificity of 88%.…”

The Bladder EpiCheck Test as a Non-Invasive Tool Based on the Identification of DNA Methylation in Bladder Cancer Cells in the Urine: A Review of Published Evidence

“…No gender limit was considered. Two studies [10,11] included only patients with NMIBC resected within the previous 12 months.…”

“…Particularly, for cytological specimen classification, all studies used the Paris System for Reporting Urinary Cytology. During three of the studies [10,11,17] the wash cytology was considered 'negative' when the result was 'negative for high-grade urothelial carcinoma (HGUC)' and 'atypical urothelial cells', whereas 'suspicious for HGUC', 'HGUC', and 'low-grade (LG) intraepithelial neoplasia' were clustered as 'positive'. Concerning the case of positive spontaneous or wash cytology with negative cystoscopy and/or histology, the reference standard was evaluated at the subsequent follow-up cystoscopy with multiple random biopsies or targeted biopsies on a suspicious area [17].…”