A Urine Based Genomic Assay to Triage Patients with Hematuria for Cystoscopy

No AccessJournal of UrologyAdult Urology1 Jul 2020A Urine Based Genomic Assay to Triage Patients with Hematuria for CystoscopyThis article is commented on by the following:Editorial CommentEditorial Comment Kim E. M. van Kessel, Joep J. de Jong, Angelique C. J. Ziel-van der Made, Hossain Roshani, Stefan M. Haensel, Josien H. Wolterbeek, Egbert R. Boevé, Eric H. G. M. Oomens, Niels J. van Casteren, Manuel Krispin, Joost L. Boormans, Ewout W. Steyerberg, Wim van Criekinge, and Ellen C. Zwarthoff Kim E. M. van KesselKim E. M. van Kessel Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands , Joep J. de JongJoep J. de Jong Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands , Angelique C. J. Ziel-van der MadeAngelique C. J. Ziel-van der Made Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands , Hossain RoshaniHossain Roshani Department of Urology, Haga Hospital, The Hague, The Netherlands , Stefan M. HaenselStefan M. Haensel Department of Urology, Haven Hospital, Rotterdam, The Netherlands , Josien H. WolterbeekJosien H. Wolterbeek Department of Urology, Haven Hospital, Rotterdam, The Netherlands , Egbert R. BoevéEgbert R. Boevé Department of Urology, Franciscus Hospital, Rotterdam, The Netherlands , Eric H. G. M. OomensEric H. G. M. Oomens , Niels J. van CasterenNiels J. van Casteren Department of Urology, IJsselland Hospital, Capelle a/d IJssel, The Netherlands , Manuel KrispinManuel Krispin MDxHealth Inc., Irvine, California , Joost L. BoormansJoost L. Boormans Department of Urology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands , Ewout W. SteyerbergEwout W. Steyerberg Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands , Wim van CriekingeWim van Criekinge MDxHealth Inc., Irvine, California Laboratory of Bioinformatics and Computational Genomics, Ghent University, Belgium , and Ellen C. ZwarthoffEllen C. Zwarthoff §Correspondence: Department of Pathology, Erasmus MC Cancer Institute, Room Be304, P.O. Box 2040, 3000 CARotterdam , The Netherlands telephone: +31107043929; FAX: +31107044762; E-mail Address: [email protected] Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands View All Author Informationhttps://doi.org/10.1097/JU.0000000000000786AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Current clinical guidelines recommend cystoscopy in patients who present with hematuria to rule out a bladder tumor. We evaluated whether our previously developed urine assay was able to triage patients with hematuria for cystoscopy in a large prospective cohort. Materials and Methods: A urine sample was collected before cystoscopy and mutation/methylation status of 6 genes was determined on cellular DNA. The existing diagnostic model was validated on this cohort. Logistic regression was applied to investigate other potential variables. The primary end point was the model performance as indicated by the AUC. Secondary end points were sensitivity, specificity and negative predictive value. Clinical usefulness was determined by the net benefit approach. Results: In 838 patients biomarker status could be determined for all genes. Urothelial cancer was observed in 112 patients (98 of 457 in the gross and 14 of 381 in the microscopic hematuria group). Validation of the existing model resulted in an AUC of 0.93. Logistic regression analysis identified type of hematuria as a significant additional variable. Adding type of hematuria resulted in an AUC of 0.95 (96% sensitivity, 73% specificity, 99% negative predictive value). The assay identified all upper tract tumors not visible by cystoscopy (in 6). Net benefit analysis showed that the urine assay should be preferred over current clinical practice. Implementing the urine assay as a triage tool could lead to a 53% reduction in cystoscopies. Conclusions: The urine assay detected urothelial cancer with a very high accuracy and can be used to triage patients presenting with hematuria for cystoscopy. References 1. : Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol 2012; 188: 2473. Link, Google Scholar 2. : Hematuria. American College of Radiology. ACR appropriateness criteria. Radiology, suppl., 2000; 215: 841. Google Scholar 3. : Canadian guidelines for the management of asymptomatic microscopic hematuria in adults. Can Urol Assoc J 2009; 3: 77. Google Scholar 4. Nederlandse Vereniging voor Urologie: Richtlijn Hematurie, 2010. Available at https://www.nvu.nl/en-us/kwaliteit/richtlijnen/actuelerichtlijnen.aspx. Accessed April 4, 2018. 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No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byWoldu S, Ng C, Loo R, Slezak J, Jacobsen S, Tan W, Kelly J, Lough T, Darling D, van Kessel K, de Jong J, van Criekinge W, Shariat S, Hiar A, Brown S, Boorjian S, Barocas D, Svatek R and Lotan Y (2020) Evaluation of the New American Urological Association Guidelines Risk Classification for HematuriaJournal of Urology, VOL. 205, NO. 5, (1387-1393), Online publication date: 1-May-2021.Related articlesJournal of Urology13 Apr 2020Editorial CommentJournal of Urology13 Apr 2020Editorial Comment Volume 204Issue 1July 2020Page: 50-57Supplementary Materials Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.Keywordsbiomarkersmutationurinalysismethylationurinary bladder neoplasmsMetricsAuthor Information Kim E. M. van Kessel Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands Equal study contribution. More articles by this author Joep J. de Jong Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands Equal study contribution. More articles by this author Angelique C. J. Ziel-van der Made Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands More articles by this author Hossain Roshani Department of Urology, Haga Hospital, The Hague, The Netherlands More articles by this author Stefan M. Haensel Department of Urology, Haven Hospital, Rotterdam, The Netherlands More articles by this author Josien H. Wolterbeek Department of Urology, Haven Hospital, Rotterdam, The Netherlands More articles by this author Egbert R. Boevé Department of Urology, Franciscus Hospital, Rotterdam, The Netherlands More articles by this author Eric H. G. M. Oomens More articles by this author Niels J. van Casteren Department of Urology, IJsselland Hospital, Capelle a/d IJssel, The Netherlands More articles by this author Manuel Krispin MDxHealth Inc., Irvine, California Financial interest and/or other relationship with MDxHealth. More articles by this author Joost L. Boormans Department of Urology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands Financial interest and/or other relationship with MSD, Roche, BMS and Janssen Pharmaceuticals. More articles by this author Ewout W. Steyerberg Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands More articles by this author Wim van Criekinge MDxHealth Inc., Irvine, California Laboratory of Bioinformatics and Computational Genomics, Ghent University, Belgium Financial interest and/or other relationship with MDxHealth. More articles by this author Ellen C. Zwarthoff Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands §Correspondence: Department of Pathology, Erasmus MC Cancer Institute, Room Be304, P.O. Box 2040, 3000 CARotterdam , The Netherlands telephone: +31107043929; FAX: +31107044762; E-mail Address: [email protected] Equal study contribution. Financial interest and/or other relationship with MDxHealth. More articles by this author Expand All Supported by MDxHealth and powered by Health Holland, Top Sector Life Sciences & Health (https://www.health-holland.com). No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. Advertisement PDF downloadLoading ...