Combinations of Urinary Biomarkers for Surveillance of Patients with Incident Nonmuscle Invasive Bladder Cancer: The European FP7 UROMOL Project

No AccessJournal of UrologyInvestigative Urology1 May 2013Combinations of Urinary Biomarkers for Surveillance of Patients with Incident Nonmuscle Invasive Bladder Cancer: The European FP7 UROMOL Project Tahlita C.M. Zuiverloon, Willemien Beukers, Kirstin A. van der Keur, Annemieke J.M. Nieuweboer, Thomas Reinert, Lars Dyrskjot, Torben F. Orntoft, and Ellen C. Zwarthoff Tahlita C.M. ZuiverloonTahlita C.M. Zuiverloon Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands , Willemien BeukersWillemien Beukers Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands , Kirstin A. van der KeurKirstin A. van der Keur Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands , Annemieke J.M. NieuweboerAnnemieke J.M. Nieuweboer Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands , Thomas ReinertThomas Reinert Department of Molecular Medicine, Aarhus University Hospital, Denmark , Lars DyrskjotLars Dyrskjot Department of Molecular Medicine, Aarhus University Hospital, Denmark , Torben F. OrntoftTorben F. Orntoft Department of Molecular Medicine, Aarhus University Hospital, Denmark , and Ellen C. ZwarthoffEllen C. Zwarthoff Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands View All Author Informationhttps://doi.org/10.1016/j.juro.2012.11.115AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We determined a combination of markers with optimal sensitivity to detect recurrence in voided urine after resection of an incident low grade, nonmuscle invasive bladder tumor. Materials and Methods: A total of 136 patients with G1/G2 nonmuscle invasive bladder tumor were included in the study at transurethral resection of the incident tumor. At least 3 followup urine samples were required for patient selection. DNA was extracted from the incident tumor and cell pellets of subsequently collected urine samples. We performed FGFR3, PIK3CA and RAS mutation analysis, and microsatellite and methylation analysis on tissue and urine DNA samples. Results: We obtained 716 urine samples. The 136 patients experienced a total of 552 recurrences during a median 3-year followup. Sensitivity for detecting a recurrent tumor varied between 66% and 68% for the molecular tests after patient stratification based on tumor DNA analysis. A combination of markers increased sensitivity but decreased the number of patients eligible for a certain test combination. Combining urine cytology with FGFR3 analysis without stratifying for FGFR3 status of the incident tumor increased sensitivity from 56% to 76%. Conclusions: A combination of markers increased the percentage of patients eligible for urine based followup and the sensitivity of recurrence detection. Adding FGFR3 analysis to urine cytology could be valuable for noninvasive followup of patients with nonmuscle invasive bladder cancer. References 1 : EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol2008; 54: 303. Google Scholar 2 : Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urol2005; 174: 862. Link, Google Scholar 3 : The role of hexaminolevulinate fluorescence cystoscopy in bladder cancer. Nat Clin Pract Urol2007; 4: 542. Google Scholar 4 : The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics2003; 21: 1315. 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Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byBeukers W, van der Keur K, Kandimalla R, Vergouwe Y, Steyerberg E, Boormans J, Jensen J, Lorente J, Real F, Segersten U, Orntoft T, Malats N, Malmström P, Dyrskjot L and Zwarthoff E (2016) FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter StudyJournal of Urology, VOL. 197, NO. 6, (1410-1418), Online publication date: 1-Jun-2017. Volume 189Issue 5May 2013Page: 1945-1951Supplementary Materials Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordsreceptor, fibroblast growth factor, type 3neoplasm recurrencebiological markersurinary bladderurinary bladder neoplasmsMetricsAuthor Information Tahlita C.M. Zuiverloon Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands Equal study contribution. More articles by this author Willemien Beukers Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands Equal study contribution. More articles by this author Kirstin A. van der Keur Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Annemieke J.M. Nieuweboer Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Thomas Reinert Department of Molecular Medicine, Aarhus University Hospital, Denmark More articles by this author Lars Dyrskjot Department of Molecular Medicine, Aarhus University Hospital, Denmark More articles by this author Torben F. Orntoft Department of Molecular Medicine, Aarhus University Hospital, Denmark Financial interest and/or other relationship with AROS Applied Biotechnology. More articles by this author Ellen C. Zwarthoff Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Expand All Advertisement PDF downloadLoading ...