title: Use of fluorescence in situ hybridization to predict response to bacillus Calmette-Guérin therapy for bladder cancer: results of a prospective trial.
abstract: OBJECTIVE
  No reliable methods currently exist to predict patient response to intravesical immunotherapy with bacillus Calmette-Guérin given after transurethral resection for high risk nonmuscle invasive bladder cancer. We initiated a prospective clinical trial to determine whether fluorescence in situ hybridization results during bacillus Calmette-Guérin immunotherapy can predict therapy failure.
  
  
  METHODS
  Candidates for standard of care bacillus Calmette-Guérin were offered participation in a clinical trial. Fluorescence in situ hybridization was performed before bacillus Calmette-Guérin, and at 6 weeks, 3 months and 6 months during bacillus Calmette-Guérin therapy with maintenance. Cox proportional hazards regression was used to assess the relationship between fluorescence in situ hybridization results and tumor recurrence or progression. The Kaplan-Meier product limit method was used to estimate recurrence-free and progression-free survival.
  
  
  RESULTS
  A total of 126 patients participated in the study. At a median followup of 24 months 31% of patients had recurrent tumors and 14% experienced disease progression. Patients who had positive fluorescence in situ hybridization results during bacillus Calmette-Guérin therapy were 3 to 5 times more likely than those who had negative fluorescence in situ hybridization results to experience recurrent tumors and 5 to 13 times more likely to have disease progression (p <0.01). The timing of positive fluorescence in situ hybridization results also affected outcomes. For example, patients with a negative fluorescence in situ hybridization result at baseline, 6 weeks and 3 months demonstrated an 8.3% recurrence rate compared to 48.1% for those with a positive result at all 3 points.
  
  
  CONCLUSIONS
  Fluorescence in situ hybridization results can identify patients at risk for tumor recurrence and progression during bacillus Calmette-Guérin immunotherapy. This information may be used to counsel patients about alternative treatment strategies.
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. akamat@mdanderson.org
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.forename: Rian J
authors.initials: RJ
authors.lastname: Dickstein
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Messetti
authors.forename: Roosevelt
authors.initials: R
authors.lastname: Anderson
authors.forename: Shanna M
authors.initials: SM
authors.lastname: Pretzsch
authors.forename: Graciela Noguera
authors.initials: GN
authors.lastname: Gonzalez
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Katz
authors.forename: Abha
authors.initials: A
authors.lastname: Khanna
authors.forename: Tanweer
authors.initials: T
authors.lastname: Zaidi
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000368:Aged; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine