title: Fibroblast growth factor receptor 3 mutation analysis on voided urine for surveillance of patients with low-grade non-muscle-invasive bladder cancer.
abstract: OBJECTIVE
  Mutations in the fibroblast growth factor receptor 3 (FGFR3) have been found in 70% of the low-grade non-muscle-invasive bladder cancer (NMI-BC) tumors. We aim to determine the potential of FGFR3 mutation analysis on voided urine to detect recurrences during surveillance of patients with low-grade NMI-BC.
  
  
  METHODS
  FGFR3 mutation status of the study inclusion tumor was determined from 200 low-grade NMI-BC patients. Patients with an FGFR3-mutant inclusion tumor were selected for analysis and monitored by cystoscopy, and voided urine samples were collected. FGFR3 mutation analysis was done on 463 prospectively collected urines. Sensitivity and predictive value of the assay were determined for detection of concomitant recurrences. Longitudinal and Cox time-to-event analyses were done to determine the predictive value for detection of future recurrences.
  
  
  RESULTS
  Median follow-up was 3.5 years. The sensitivity of the assay for detection of concomitant recurrences was 26 of 45 (58%). Of the 105 positive urine samples, 85 (81%) were associated with a concomitant or a future recurrence. An FGFR3-positive urine was associated with a 3.8-fold (P < 0.0001) higher risk of having a recurrence in the Cox analysis. In contrast, only 41 of 358 (11%) FGFR3-negative urine samples were associated with a recurrence. Positive predictive value increased from 25% to 90% in patients having consecutive FGFR3-positive urine tests.
  
  
  CONCLUSIONS
  FGFR3 mutation analysis on voided urine is a simple and noninvasive diagnostic method for detection of recurrences during surveillance of patients presenting with a low-grade FGFR3-mutant NMI-BC tumor.
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Tahlita C M
authors.initials: TC
authors.lastname: Zuiverloon
authors.forename: Madelon N M
authors.initials: MN
authors.lastname: van der Aa
authors.forename: Theo H
authors.initials: TH
authors.lastname: van der Kwast
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000652:urine*; D012008:Recurrence; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000652:urine*
chemical_list: D051498:Receptor, Fibroblast Growth Factor, Type 3