Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial

被引:122
作者
Witjes, J. Alfred [1 ]
Morote, Juan [2 ]
Cornel, Erik B. [3 ]
Gakis, Georgios [4 ]
van Valenberg, F. Johannes P. [1 ]
Lozano, Fernando [2 ]
Sternberg, Itay A. [5 ]
Willemsen, Ellen [3 ]
Hegemann, Miriam L. [6 ]
Paitan, Yossi [7 ]
Leibovitch, Ilan [5 ]
机构
[1] Radboud Univ Nijmegen, Dept Urol, Med Ctr, POB 9101, NL-6500 HB Nijmegen, Netherlands
[2] Hosp Univ Vall dHebron Hosp, Dept Urol, Barcelona, Spain
[3] ZGT Med Ctr, Dept Urol, Hengelo, Netherlands
[4] Univ Hosp Wurzburg, Dept Urol & Pediat Urol, Wurzburg, Germany
[5] Meir Med Ctr, Dept Urol, Kefar Sava, Israel
[6] Sindelfingen Boblingen Hosp, Dept Urol, Sindelfingen, Germany
[7] Meir Med Ctr, Clin Microbiol Lab, Kefar Sava, Israel
来源
EUROPEAN UROLOGY ONCOLOGY | 2018年 / 1卷 / 04期
关键词
Detection; Follow up; Negative predictive value; Non-muscle-invasive bladder cancer; Surveillance; Urinary biomarker; IN-SITU; METAANALYSIS; CYSTOSCOPY; DIAGNOSIS; CYTOLOGY; BURDEN;
D O I
10.1016/j.euo.2018.06.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The highly frequent strategy of surveillance for non-muscle-invasive bladder cancer (NMIBC) involves cystoscopy and cytology. Urine assays currently available have not shown performance sufficient to replace the current gold standard for follow-up, which would require a very high negative predictive value (NPV), especially for high-grade tumors. Bladder EpiCheck (BE) is a novel urine assay that uses 15 proprietary DNA methylation biomarkers to assess the presence of bladder cancer. Objective: To assess the performance of BE for NMIBC recurrence. Design, setting, and participants: This was a blinded, single-arm, prospective multicenter study. The inclusion criteria were age >= 22 yr, urothelial carcinoma (UC) being monitored cystoscopically at 3-mo intervals, all UC resected within 12 mo, able to produce 10 ml of urine, and able to consent. Outcome measurements and statistical analysis: The BE test characteristics were calculated and compared to cytology and cystoscopy results confirmed by pathology. Results and limitations: Out of 440 patients recruited, 353 were eligible for the performance analysis. Overall sensitivity, specificity, NPV, and positive predictive value were 68.2%, 88.0%, 95.1%, and 44.8%, respectively. Excluding low-grade (LG) Ta recurrences, the sensitivity was 91.7% and NPV was 99.3%. The area under receiver operating characteristic (ROC) curves with and without LG Ta lesions was 0.82 and 0.94, respectively. Conclusions: In follow-up of NMIBC patients, the BE test showed an overall high NPV of 95.1%, and 99.3% when excluding LG Ta recurrences. With high specificity of 88.0%, the test could be incorporated in NMIBC follow-up since high-grade recurrences would be instantly detected with high confidence. Thus, the current burden of repeat cystoscopies and cytology tests could be reduced. Patient summary: The Bladder EpiCheck urine test has a clinically relevant and high negative predictive value. Its use in clinical routine could reduce the number of follow-up cystoscopies, and thus associated patient and financial burdens. (C) 2018 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
引用
收藏
页码:307 / 313
页数:7
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