Presentation Authors: J Alfred Witjes*, Nijmegen, Netherlands, Fernando Lozano, Barcelona, Spain, Ilan Leibovitch, Kfar Saba, Israel, Erik B Cornel, Hengelo, Netherlands, Joyce Baard, Amsterdam, Netherlands, Georgios Gakis, Würzburg, Germany, Mario Alvarez-Maestro, Madrid, Spain, Hans van Valenberg, Nijmegen, Netherlands, Itay Sternberg, Kfar Saba, Israel, Ellen Willemsen, Hengelo, Netherlands, Leonore F. Albers, Amsterdam, Netherlands, Miriam Lena Hegemann, Sindelfingen, Germany, Yossi Paitan, Kfar Saba, Israel, Juan Morote, Barcelona, Spain
Introduction: The first goal of NMIBC monitoring is to promptly detect and treat high-grade (HG) tumors. This mandates high negative predictive value (NPV) if a urine biomarker is considered to replace part of standard follow up cystoscopies and cytologies. Bladder EpiCheck (BE) is a methylation-based urine marker for bladder cancer monitoring that demonstrated outstanding results in non low-grade (LG) tumors in the first analysis of its European multicenter study: sensitivity 91.7% and NPV 99.3% over specificity of 88.0% in 440 patients(1). The study continued recruiting, and this is its 2nd analysis._x000D_
(1)Witjes et al. EUO 2018;1:307-313
Methods: This was a multicenter, prospective, blinded, single arm, single visit, cohort study performed in 7 centers in Europe and Israel under IRB. Inclusion criteria: Age >=22y, urothelial carcinoma undergoing cystoscopic surveillance at 3 months intervals, all UC resected within 12mths, able to produce 10 mL of urine, able to consent. Exclusion criteria: Planning to undergo radical cystectomy or chemotherapy-radiation for UC. BE is a urine assay using 15 proprietary methylation biomarkers to assess the presence of bladder cancer.
Results: The demographic data was representative of NMIBC patients (Table 1.). Out of 822 patients, 81 did not have BE results and additional 84 did not have a definitive reference standard diagnosis of positive/negative. The final cohort for analysis had 657 patients: 80 positive (36 LG, 40 HG, 4 no path) and 577 negative._x000D_
Study Endpoints are presented in Figure 1 alongside the results from the first analysis. The results were similar between the two analyses in all parameters.Sensitivity by grade of BE, cytology and cystoscopy are presented in figure 2. BE outperformed cytology in all categories (all-grade, LG and non-LG tumors). Cystoscopy outperformed BE and cytology in all-grades and LG tumors detection.
Conclusions: Consistent outstanding results with NPV of 99% in a large cohort further substantiates the evidence of BE as a robust rule-out test for high-grade cancers. Such high NPV with high specificity allows to safely utilize BE in NMIBC monitoring, even as an alternative to the standard methods that demonstrated inferior (cytology) or similar (cystoscopy) performance in this cohort.
Source of Funding: Nucleix