title: Multicenter evaluation of the role of UroVysion FISH assay in surveillance of patients with bladder cancer: does FISH positivity anticipate recurrence?
abstract: BACKGROUND
  The significance of a positive UroVysion FISH assay is uncertain in patients with normal cystoscopy. This multicenter study evaluates the clinical significance of a positive FISH assay in patients with no visible tumor and excluding those with a positive cytology.
  
  
  METHODS
  A multi-institutional, retrospective study of patients with a history of urothelial carcinoma of the bladder identified 664 patients with a FISH assay after excluding those with cystoscopic evidence of a tumor and/or positive cytology. Our primary end point was cancer recurrence, defined by biopsy. Progression was defined as recurrence with a tumor stage ≥T2. Statistical analyses were performed using Fisher's exact test as a one-tailed test and Chi-square test with significance at 0.05, using SPSS(®) version 19.0 (SPSS Inc., Chicago, IL, USA).
  
  
  RESULTS
  Of the 664 patients in this study, tumor stage was Ta (363, 55 %), T1 (183, 28 %), and CIS (109, 16 %) and most were high grade (440 pts, 66 %). The median follow-up was 26 months (3-104 months), and 277 (41.7 %) patients were recurred. In patients who were FISH positive, mean time to recurrence was 12.6 months, compared to 17.9 months if FISH negative (p = 0.03). In univariate analysis, atypical cytology, positive FISH, cystoscopic findings (atypical vs. normal), and previous intravesical therapy were associated with recurrence (p < 0.05). On multivariate analysis, pathologic stage, cystoscopic findings, and cytology were independently associated with recurrence (p < 0.05). Progression to ≥T2 disease occurred in 34 (5.1 %) patients in this cohort. On multivariate analysis, only initial T stage and FISH result were found to be independent predictors of progression (p < 0.05).
  
  
  CONCLUSIONS
  Patients with a positive FISH and atypical cytology are more likely to recur even in the absence of visible tumor. FISH positivity may portend a higher risk for progression. These findings require prospective validation.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Seideman
authors.forename: Daniel
authors.initials: D
authors.lastname: Canter
authors.forename: Philip
authors.initials: P
authors.lastname: Kim
authors.forename: Billy
authors.initials: B
authors.lastname: Cordon
authors.forename: Alon
authors.initials: A
authors.lastname: Weizer
authors.forename: Irma
authors.initials: I
authors.lastname: Oliva
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.forename: Brant A
authors.initials: BA
authors.lastname: Inman
authors.forename: Michael
authors.initials: M
authors.lastname: Posch
authors.forename: Harry
authors.initials: H
authors.lastname: Herr
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D003558:Cystoscopy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D055815:Young Adult