title: Recurrence and progression in patients with non-muscle invasive bladder cancer: prognostic models including multicolor fluorescence in situ hybridization molecular grading.
abstract: OBJECTIVE
  To test the prognostic value of multicolor fluorescence in situ hybridization analyses of tumor cells in urine for prediction of the recurrence and progression of tumor in patients with intermediate risk non-muscle invasive bladder cancer.
  
  
  METHODS
  A total of 168 patients with non-muscle invasive bladder cancer were included in the study. Fluorescence in situ hybridization was carried out on the bladder wash urine collected before resection. Tumors were classified as low molecular grading if they had a diploid chromosomal pattern or only a loss of p16 or ch3 aneuploidy, and as high molecular grading if they showed aneuploidy of ch7 or 17. Cox regression models assessed the added prognostic value of fluorescence in situ hybridization for primary tumor recurrence or progression, respectively.
  
  
  RESULTS
  Median follow up was 67 months. A total of 57% of tumors were classified as low molecular grading. The 2- and 5-year recurrence-free survival was 68% and 49% for low molecular grading, and 47% and 30% for high molecular grading, respectively. The 2- and 5-year progression-free survival was 95% and 84% for low molecular grading, and 79% and 58% for high molecular grading tumor patients, respectively. Molecular grading (hazard ratio 1.60; P = 0.03) was associated with recurrence, when also accounting for histopathology and a patient's characteristics. Both cancer severity score (hazard ratio 1.51; P < 0.01) and molecular grading (hazard ratio 2.53; P < 0.01) independently and positively predicted progression in multivariable models. The C-index for predicting recurrence increased from 0.58 to 0.61 when molecular grading fluorescence in situ hybridization was included in the model, and from 0.68 to 0.72 when predicting progression.
  
  
  CONCLUSIONS
  Fluorescence in situ hybridization-based molecular grading increases the accuracy of a prognostic model, predicting both recurrence and progression in patients with intermediate risk non-muscle invasive bladder cancer.
authors.affiliation: Department of Urology, General Hospital of Bolzano, Bolzano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Lodde
authors.forename: Christine
authors.initials: C
authors.lastname: Mian
authors.forename: Roman
authors.initials: R
authors.lastname: Mayr
authors.forename: Evi
authors.initials: E
authors.lastname: Comploj
authors.forename: Emanuela
authors.initials: E
authors.lastname: Trenti
authors.forename: Roberto
authors.initials: R
authors.lastname: Melotti
authors.forename: Fabio
authors.initials: F
authors.lastname: Campodonico
authors.forename: Massimo
authors.initials: M
authors.lastname: Maffezzini
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Armin
authors.initials: A
authors.lastname: Pycha
mesh_terms: D000368:Aged; D000782:Aneuploidy; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D003116:Color; D004171:Diploidy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology*; D016016:Proportional Hazards Models; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D014556:Urine / Q000166:cytology
keywords: multicolor fluorescence in situ hybridization; non-muscle invasive bladder cancer; prognostic model; progression; recurrence