title: p53 predictive value for pT1-2 N0 disease at radical cystectomy.
abstract: OBJECTIVE
  Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB.
  
  
  METHODS
  In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality.
  
  
  RESULTS
  In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively.
  
  
  CONCLUSIONS
  Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA. sfshariat@gmail.com
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Hendrik
authors.initials: H
authors.lastname: Isbarn
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Nielsen
authors.forename: Umberto
authors.initials: U
authors.lastname: Capitanio
authors.forename: Claudio
authors.initials: C
authors.lastname: Jeldres
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.forename: George
authors.initials: G
authors.lastname: Netto
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cote
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000601:surgery; D015331:Cohort Studies; D015653:Cystectomy; D005260:Female; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000601:surgery