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.

Abstract

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 10ml 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.

• Authors: J Alfred Witjes, Juan Morote, Erik B Cornel, Georgios Gakis, F Johannes P van Valenberg, Fernando Lozano, Itay A Sternberg, Ellen Willemsen, Miriam L Hegemann, Yossi Paitan, Ilan Leibovitch
• Journal: European urology oncology (Eur Urol Oncol) Vol. 1 Issue 4 Pg. 307-313 (09 2018) ISSN: 2588-9311 [Electronic] Netherlands
• PMID: 31100252 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis, urine)
• Carcinoma, Squamous Cell (diagnosis, genetics, pathology, urine)
• DNA Methylation
• Female
• Humans
• Male
• Middle Aged
• Monitoring, Physiologic (methods)
• Predictive Value of Tests
• Sensitivity and Specificity
• Urinalysis (methods, standards)
• Urinary Bladder (metabolism, pathology)
• Urinary Bladder Neoplasms (diagnosis, genetics, pathology, urine)
• Watchful Waiting (methods)