North American study and meta-analysis evaluating performance of Bladder EpiCheck <sup>®</sup> , a FDA cleared test, in non-muscle invasive bladder cancer recurrence
Neil Fleshner, H. Barton Grossman, Ryan K. Berglund, Jason Hafron, Brant A. Inman, Lawrence I. Karsh, Kelvin A. Moses, Daniel R. Saltzstein, Anup Shah, Jonathan L. Wright, J. Alfred Witjes, Yair Lotan
Abstract
Background: Bladder EpiCheck (BE) is a novel methylation-based PCR urine test for the detection of non-muscle invasive bladder cancer (NMIBC) recurrences. Objective: We present the results of a North American study evaluating BE and meta-analysis of literature. Methods: A prospective, blinded, multicenter study was conducted in North America. Voided urine was collected from NMIBC patients prior to cystoscopic surveillance. BE testing was performed centrally. For the meta-analysis, a PUBMED search was performed to identify all published peer-reviewed clinical studies of BE for NMIBC surveillance. Results: In this study, 674 patients were enrolled of which 449 were included. Overall sensitivity was 67% (95%CI 58%-74%), specificity was 84% (80%-88%), PPV was 65% (57%-73%) and NPV was 85% (81%-89%). For high-grade (HG) recurrence, sensitivity was 77% (65%-85%) and NPV was 95% (92%-97%).In patients with negative cystoscopy and cytology at the first study visit, risk of subsequent recurrence in 12 months was 5.3 (2.7-10.3) times higher in patients with positive BE vs. negative BE (p < 0.0001). In patients with negative cystoscopy and equivocal cytology, BE was positive in 75-89% of those with later HG recurrence, with PPV of 42% (15%-72%)-63% (38%-84%).The meta-analysis included 7 studies and 1564 patients. Overall sensitivity was 82% (66-92%), HG sensitivity was 91% (82-95%), specificity was 85% (80-88%), PPV was 60% (55-64%) and HG NPV was 98% (97-99%). Conclusions: The consistently strong performance of BE indicate that a positive test could improve timely disease recurrence detection and a negative test could rule-out HG disease. Furthermore, the low rate of false positive results, potentially minimizes unnecessary downstream procedures and patient anxiety.