Introduction: Non-invasive tests based on DNA methylation profiles in the urine have been introduced as a possible alternative to cystoscopies, such as the Bladder EpiCheck (BE) test.
Methods: In this single-center prospective study we included patients (pts) on follow-up (FU) for any-risk BC who underwent cystoscopy between 01/2019 and 02/2020. Pts with positive pathology results were considered positive according to the reference standard (RS). In case of positive cystoscopy, we considered the result of the subsequent endoscopic resection. In case of negative/inconclusive pathology result and positive cytology, the RS was evaluated at the subsequent operative cystoscopy. Pts without pathology/cytology were excluded. DNA methylation status was analyzed after urine centrifugation. An EpiScore = 60 was considered positive. We performed a sensitivity analysis testing the performance of the BE for the detection of high-grade (HG)/any-grade (AG) BC. A multivariable logistic regression analysis assessed the association between BE and AG/HG BC.
Results: We included 120 pts. 33 (27%) pts had a BC recurrence. Median (IQR) FU was 25 (24-29) mths. 22 (18%) pts without an RS were excluded from the study. Mean EpiScore was 41(SD:31). 45/98 (46%) pts were positive according to the RS. 34/98(35%) had a positive and 64/98(65%) a negative BE result. Among the positive pts, 27(79%) were the true positive tests, 7(21%) were false positives. Among pts with a negative BE result, 47(73%) were the true negative, and 17 (27%) were false-negative. None of the true negatives relapsed at FU. All HG BCs but 2 had a positive BE test. Overall sensitivity was 61%( 95% confidence interval-CI:21-92); specificity was 87%(95%CI:40-100). The overall negative predictive value (NPV) was 73%(95%CI:29-97), the positive (PPV) was 79%(95%CI:33-98). Excluding low-grades (LG), sensitivity, specificity, PPV and NPV were 79% (95%CI:33-98), 89% (95%CI:41-100), 77%(95%CI:31-97) and 90%(95%CI:42-100). For LG BC, sensitivity, specificity, PPV and NPV were 27% (95%CI:4-53), 21% (95%CI:3-48), 15% (9-44) and 65%(95%CI:46-81). An increase in 1 EpiScore corresponded to a 5% increase in the risk of harboring an HG BC. On multivariable logistic regression analysis, BE was independently associated with the presence of AG(OR:14;95%CI:6-43;p < 0.001) and HG BC (OR:20;95%CI:3-126;p < 0.001). The AUC was 81%(95%CI:73-89) for AG BC, and 96%(95%CI:88-100) for HG BC.
Conclusions: BE showed high diagnostic performance in HG BC.
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