title: Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guérin.
abstract: OBJECTIVE
  To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) treated with intravesical Bacille Calmette-Guérin (BCG) therapy.
  
  
  METHODS
  This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC (high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy) treated with transurethral resection (TUR) and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 (MMP9) using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves.
  
  
  RESULTS
  Median follow-up was 88 months (mean, 99; range, 14-212 months). The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence (P value 0.03 and 0.02, respectively), although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence (log rank P values <0.001, 0.03, 0.02, and 0.006, respectively) and when associated with positive MMP9 or p21, it was significantly correlated to progression (log rank P values 0.01 and 0.04, respectively).
  
  
  CONCLUSIONS
  Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings.
authors: Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Canada.
authors: Sultan S
authors: SS
authors: Alkhateeb
authors: Mischel
authors: M
authors: Neill
authors: Sas
authors: S
authors: Bar-Moshe
authors: Bas Van
authors: BV
authors: Rhijn
authors: David M
authors: DM
authors: Kakiashvili
authors: Neil
authors: N
authors: Fleshner
authors: Michael
authors: M
authors: Jewett
authors: Michel
authors: M
authors: Petein
authors: Claude
authors: C
authors: Schulman
authors: Sally
authors: S
authors: Hanna
authors: Peter J
authors: PJ
authors: Bostrom
authors: Thierry
authors: T
authors: Roumeguere
authors: Shahrokh F
authors: SF
authors: Shariat
authors: Sandrine
authors: S
authors: Rorive
authors: Alexandre R
authors: AR
authors: Zlotta