Dataset Information

Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer.

ABSTRACT:

Objectives

To investigate prospectively the clinical utility and influence on decision-making of Bladder EpiCheck™, a non-invasive urine test, in the surveillance of non-muscle-invasive bladder cancer (NMIBC).

Materials and methods

Urine samples from 440 patients undergoing surveillance for NMIBC were prospectively collected at five centres and evaluated using the Bladder EpiCheck test (NCT02647112). A multivariable nomogram and decision-curve analysis (DCA) were used to evaluate the impact of Bladder EpiCheck on decision-making when used in routine clinical practice. The test was designed to exclude recurrent disease.

Results

Data from 357 patients were available for analysis. The test had a specificity of 88% (95% confidence interval [CI] 84-91), a negative predictive value (NPV) of 94.4% (95% CI 91-97) for the detection of any cancer and an NPV of 99.3% for the detection of high-grade cancer. In multivariable analysis, positive Bladder EpiCheck results were independently associated with any and high-grade disease recurrence (odds ratio [OR] 18.1, 95% CI 8.7-40.2; P < 0.001 and OR 78.3, 95% CI 19.2-547; P < 0.001). The addition of Bladder EpiCheck to standard variables improved its predictive ability for any and high-grade disease recurrence by a difference of 16% and 22%, respectively (area under the curve 85.9% and 96.1% for any and high-grade cancer, respectively). DCA showed an improvement in the net benefit relative to cystoscopy over a large threshold of probability, resulting in a significant reduction in unnecessary investigations. These results were similar in subgroups assessing the impact of specific clinical features.

Conclusions

Bladder EpiCheck is a robust high-performing diagnostic test in patients with NMIBC undergoing surveillance that can potentially reduce the number of unnecessary investigations.

SUBMITTER: D'Andrea D

PROVIDER: S-EPMC6850401 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer.

D'Andrea David D Soria Francesco F Zehetmayer Sonja S Gust Kilian M KM Korn Stephan S Witjes J Alfred JA Shariat Shahrokh F SF

BJU international 20190205 6

<h4>Objectives</h4>To investigate prospectively the clinical utility and influence on decision-making of Bladder EpiCheck™, a non-invasive urine test, in the surveillance of non-muscle-invasive bladder cancer (NMIBC).<h4>Materials and methods</h4>Urine samples from 440 patients undergoing surveillance for NMIBC were prospectively collected at five centres and evaluated using the Bladder EpiCheck test (NCT02647112). A multivariable nomogram and decision-curve analysis (DCA) were used to evaluate ...[more]

PMID: 30653818

Similar Datasets

Project description:Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.

Dataset Information

Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer.

Objectives

Materials and methods

Results

Conclusions

Publications

Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets