title: FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study.
abstract: Patients with nonmuscle invasive bladder cancer are followed with frequent cystoscopies. In this study FGFR3, TERT and OTX1 were investigated as a diagnostic urinary marker combination during followup of patients with primary nonmuscle invasive bladder cancer.
  
  
  
  In this international, multicenter, prospective study 977 patients with nonmuscle invasive bladder cancer were included. A total of 2,496 urine samples were collected prior to cystoscopy during regular visits. Sensitivity was estimated to detect concomitant recurrences. Kaplan-Meier curves were used to estimate the development of future recurrences after urinalysis and a negative cystoscopy.
  
  
  
  Sensitivity of the assay combination for recurrence detection was 57% in patients with primary low grade, nonmuscle invasive bladder cancer. However, sensitivity was 83% for recurrences that were pT1 or muscle invasive bladder cancer. Of the cases 2% progressed to muscle invasive bladder cancer. Sensitivity for recurrence detection in patients with primary high grade disease was 72% and 7% of them had progression to muscle invasive bladder cancer. When no concomitant tumor was found by cystoscopy, positive urine samples were more frequently followed by a recurrence over time compared to a negative urine sample (58% vs 36%, p <0.001). High stage recurrences were identified within 1 year after a positive urine test and a negative cystoscopy.
  
  
  
  Recurrences in patients with primary nonmuscle invasive bladder cancer can be detected by a combination of urine assays. This study supports the value of urinalysis as an alternative diagnostic tool in patients presenting with low grade tumors and as a means to identify high stage tumors earlier.
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Willemien
authors.initials: W
authors.lastname: Beukers
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Kirstin A
authors.initials: KA
authors.lastname: van der Keur
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Raju
authors.initials: R
authors.lastname: Kandimalla
authors.affiliation: Department of Public Health, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Vergouwe
authors.affiliation: Department of Public Health, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Department of Urology, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Joost L
authors.initials: JL
authors.lastname: Boormans
authors.affiliation: Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jorgen B
authors.initials: JB
authors.lastname: Jensen
authors.affiliation: Servei d'Urologia, Hospital del Mar, Barcelona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain; Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Centre-CNIO, Madrid, Spain.
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Segersten
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Torben F
authors.initials: TF
authors.lastname: Orntoft
authors.affiliation: Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Centre-CNIO, Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Malats
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Dyrskjot
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands. Electronic address: e.zwarthoff@erasmusmc.nl.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D003558:Cystoscopy; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000473:pathology / Q000652:urine*; D051857:Otx Transcription Factors / Q000652:urine*; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000652:urine*; D019098:Telomerase / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; C497655:OTX1 protein, human; D051857:Otx Transcription Factors; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C509186:TERT protein, human; D019098:Telomerase
keywords: cystoscopy; local; neoplasm recurrence; neoplasm invasiveness; urinalysis; urinary bladder neoplasms