Performance Characteristics of a Multigene Urine Biomarker Test for Monitoring for Recurrent Urothelial Carcinoma in a Multicenter Study

No AccessJournal of UrologyAdult Urology1 Jun 2017Performance Characteristics of a Multigene Urine Biomarker Test for Monitoring for Recurrent Urothelial Carcinoma in a Multicenter Study Laimonis Kavalieris, Paul O'Sullivan, Chris Frampton, Parry Guilford, David Darling, Elsie Jacobson, James Suttie, Jay D. Raman, Shahrokh F. Shariat, and Yair Lotan Laimonis KavalierisLaimonis Kavalieris Pacific Edge Ltd., Dunedin, New Zealand , Paul O'SullivanPaul O'Sullivan Pacific Edge Ltd., Dunedin, New Zealand , Chris FramptonChris Frampton Department of Medicine, University of Otago, Christchurch, New Zealand , Parry GuilfordParry Guilford Pacific Edge Ltd., Dunedin, New Zealand Department of Biochemistry, University of Otago, Dunedin, New Zealand , David DarlingDavid Darling Pacific Edge Ltd., Dunedin, New Zealand , Elsie JacobsonElsie Jacobson Pacific Edge Ltd., Dunedin, New Zealand , James SuttieJames Suttie Pacific Edge Ltd., Dunedin, New Zealand , Jay D. RamanJay D. Raman Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania , Shahrokh F. ShariatShahrokh F. Shariat Department of Urology, Weill Cornell Medical College, Cornell University, New York, New York Department of Urology Medical University of Vienna, Vienna, Austria Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas , and Yair LotanYair Lotan Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas View All Author Informationhttps://doi.org/10.1016/j.juro.2016.12.010AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Urothelial carcinoma is associated with a high rate of recurrence. Guidelines recommend rigorous, regular surveillance programs that are invasive and expensive. This study describes a noninvasive urine test with sufficient sensitivity to rule out recurrent urothelial carcinoma, thereby reducing invasive diagnostic evaluations without compromising patient care. Methods and Materials: A total of 1,036 urine samples were prospectively collected from 763 patients undergoing routine surveillance for recurrent urothelial carcinoma of the bladder. The purpose was to develop and validate a test with combined high sensitivity and high negative predictive value. Cxbladder Monitor combines gene expression, clinical and patient data, and it is designed to rule out the presence of recurrent urothelial carcinoma. Results: Cxbladder Monitor showed an internally validated sensitivity of 0.93 with a negative predictive value of 0.97 and a test negative rate of 0.34. Sensitivity was 0.95 for recurrent disease with a high risk of progression (all high grade disease and low grade, stage T1 or greater disease) compared with 0.86 for low grade Ta disease. Subgroup analyses indicated that diagnostic performance was not significantly different in different age groups, or by gender or tumor stage. Sensitivity was not affected by adjuvant bacillus Calmette-Guérin treatment within the last 6 months. False-negative findings were reported in fewer than 1.5% of all samples collected. Conclusions: The Cxbladder Monitor test offers combined high sensitivity and high negative predictive value to rule out urothelial carcinoma. This test has clinical utility as a confirmatory negative adjunct to cystoscopy, potentially justifying the postponement/avoidance of cystoscopic investigations to monitor recurrence in patients. References 1 : Cancer statistics, 2016. CA Cancer J Clin2016; 66: 7. Google Scholar 2 : Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. 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Google Scholar © 2017 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byLotan Y, Raman J, Konety B, Daneshmand S, Schroeck F, Shariat S, Black P, de Lange M, Asroff S, Goldfischer E, Efros M, Chong K, Huang E, Chua H, Wu Q, Yeow S, Lau W, Yong J and Eng M (2022) Urinary Analysis of FGFR3 and TERT Gene Mutations Enhances Performance of Cxbladder Tests and Improves Patient Risk StratificationJournal of Urology, VOL. 209, NO. 4, (762-772), Online publication date: 1-Apr-2023.Raman J, Kavalieris L, Konety B, Porten S, Daneshmand S, Lotan Y and Loo R (2021) The Diagnostic Performance of Cxbladder Resolve, Alone and in Combination with Other Cxbladder Tests, in the Identification and Priority Evaluation of Patients at Risk for Urothelial CarcinomaJournal of Urology, VOL. 206, NO. 6, (1380-1389), Online publication date: 1-Dec-2021.Chang S (2017) Re: Neutrophil-to-Lymphocyte Ratio as a Bladder Cancer Biomarker: Assessing Prognostic and Predictive Value in SWOG 8710Journal of Urology, VOL. 199, NO. 3, (607-609), Online publication date: 1-Mar-2018.Wallace E, Higuchi R, Satya M, McCann L, Sin M, Bridge J, Wei H, Zhang J, Wong E, Hiar A, Mach K, Scherr D, Egerdie R, Ohta S, Sexton W, Meng M, Weizer A, Woods M, Jansz G, Zadra J, Lotan Y, Goldfarb B and Liao J (2017) Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer DetectionJournal of Urology, VOL. 199, NO. 3, (655-662), Online publication date: 1-Mar-2018. (2017) Reply by AuthorsJournal of Urology, VOL. 199, NO. 2, (406-406), Online publication date: 1-Feb-2018. Volume 197Issue 6June 2017Page: 1419-1426 Advertisement Copyright & Permissions© 2017 by American Urological Association Education and Research, Inc.Keywordstumorbiomarkerslocalmolecular diagnostic techniquesneoplasm recurrenceurinary bladder neoplasmsurologicaldiagnostic techniquesAcknowledgmentsDr. Henry Crist, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, performed the central pathology review. Dr. Blair Hesp, Kainic Medical Communications Ltd., Dunedin, New Zealand, provided editorial assistance. Study activities, including data collection and management, were performed at Health Decisions Ltd., Raleigh, North Carolina. Urine sample analysis of 5 genes was performed at Pacific Edge Diagnostics Ltd., Dunedin, New Zealand.MetricsAuthor Information Laimonis Kavalieris Pacific Edge Ltd., Dunedin, New Zealand Financial and/or other relationship with Pacific Edge. More articles by this author Paul O'Sullivan Pacific Edge Ltd., Dunedin, New Zealand Financial and/or other relationship with Pacific Edge. More articles by this author Chris Frampton Department of Medicine, University of Otago, Christchurch, New Zealand More articles by this author Parry Guilford Pacific Edge Ltd., Dunedin, New Zealand Department of Biochemistry, University of Otago, Dunedin, New Zealand Financial and/or other relationship with Pacific Edge. More articles by this author David Darling Pacific Edge Ltd., Dunedin, New Zealand Financial and/or other relationship with Pacific Edge. More articles by this author Elsie Jacobson Pacific Edge Ltd., Dunedin, New Zealand Financial and/or other relationship with Pacific Edge. More articles by this author James Suttie Pacific Edge Ltd., Dunedin, New Zealand Financial and/or other relationship with Pacific Edge. More articles by this author Jay D. Raman Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania Financial and/or other relationship with Pacific Edge. More articles by this author Shahrokh F. Shariat Department of Urology, Weill Cornell Medical College, Cornell University, New York, New York Department of Urology Medical University of Vienna, Vienna, Austria Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas More articles by this author Yair Lotan Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Financial and/or other relationship with Pacific Edge. More articles by this author Expand All Advertisement PDF downloadLoading ...