The noninvasive molecular test for detecting recurrent urothelial carcinoma also demonstrates high negative predictive value in a prospective study.
An advanced noninvasive molecular diagnostic test for detecting recurrent urothelial carcinoma (Cxbladder Monitor) demonstrated high sensitivity and a high negative predictive value (NPV) in a recently published prospective study.
Its performance was investigated using 1,036 urine samples prospectively collected from 763 patients undergoing routine surveillance. The analyses showed that the test had 93% sensitivity and a 97% NPV (J Urol [epub ahead of print] Dec. 14, 2016).
Findings of another study accepted for publication in Urologic Oncology showed that the quantitative, objective test outperformed cytology and all other comparator FDA-approved urine-based tests for ruling out recurrent urothelial carcinoma (UC).
Yair Lotan, MD, of UT Southwestern Medical Center in Dallas, is the senior author of the Journal of Urology paper and first author of the Urologic Oncology paper. He told Urology Times, “The Cxbladder Monitor test was designed to serve as a ‘rule-out’ test to maximize sensitivity. The advantage of such a test is that it rarely misses cancer, and it does much better than other tests such as cytology and NMP22 for detecting low-grade tumors. The disadvantage is that a ‘positive’ test is frequently not associated with cancer.
“Physicians should be aware that because the positive predictive value of Cxbladder Monitor is low, a positive test should not provoke a high level of anxiety,” he said.
“The clinical utility of a diagnostic tool depends on it having both high sensitivity and high NPV,” said David Darling, a co-author on both studies and chief executive officer of Pacific Edge Ltd., the maker of the test. “The study published in the Journal of Urology is the first peer-reviewed clinical evaluation of Cxbladder Monitor, and the results show that the test provides clinically meaningful results.
“Based on the performance of Cxbladder Monitor, we believe it could be used as the preferred adjunct to cystoscopy in surveillance of patients for recurrent UC, replacing other urine-based tests. In addition, as a confirmatory negative adjunct to cystoscopy, Cxbladder Monitor could reduce the need for additional investigations. Furthermore, it may also be considered as a monitoring tool for patients who may not tolerate cystoscopy for medical or religious reasons,” Darling said.
Cxbladder Monitor uses an algorithm that combines patient clinical characteristics with measurement of gene expression from urothelial cells in urine. Via RT-qPCR, it quantifies mRNA expression of five genetic biomarkers that were previously clinically validated in a test for initial diagnosis of urothelial carcinoma (Cxbladder Detect) in patients with hematuria.
Further analyses in the Journal of Urology study showed Cxbladder Monitor had 95% sensitivity for detecting recurrent disease with a high risk of progression (defined as all high-grade disease or low grade, stage ≥T1), as well as high sensitivity of 86% for detecting low-grade Ta disease, which also outperformed the other comparator tests. In addition, Cxbladder Monitor’s diagnostic performance was similar regardless of patient age, gender, and tumor stage. History of intravesical bacillus Calmette-GuÃ©rin treatment within the previous 6 months did not alter the test’s sensitivity. The rate of false-negative results was <1.5%.
The Urologic Oncology study comparing Cxbladder Monitor with other noninvasive urine tests for ruling out recurrent UC analyzed >1,000 urine samples provided by more than 800 patients undergoing surveillance for recurrent UC. Patients were recruited over a 3-year period from urology practices across the U.S. In this study, Cxbladder Monitor demonstrated 91% sensitivity and 96% NPV. Sensitivity of the other tests studied (cytology, NMP22 enzyme-linked immunosorbent assay, NMP22 BladderChek, UroVysion FISH) ranged from 11% to 36%, and the NPV for the other tests ranged from 86% to 92%. There were 14 false negative results with Cxbladder Monitor, and all of those samples also tested negative with each of the other tests.
Dr. Lotan said it is still not clear how to treat patients with a positive biomarker test in the setting of a normal cystoscopy. In that situation and considering available evidence, an intraoperative biopsy is likely not indicated based on a positive result from any commercially available biomarker test. Speaking specifically about Cxbladder Monitor, he said, “The role of this test in clinical practice still needs to be clarified. Used in conjunction with cystoscopy, a negative result can be reassuring. It may also be of value in patients at low or intermediate risk for recurrence who want to avoid cystoscopy, but the safety of avoiding cystoscopy in this setting will need to be verified.”
Cxbladder was recently included in the Federal Supply Schedule and covered by TriCare, and is currently being adopted by VA Centers across the U.S.
Dr. Lotan has consulted with Pacific Edge, primarily on study design and cost issues. Several of the authors of both studies have a financial and/or other relationship with Pacific Edge.
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