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Alkhateeb SS, Neill M, Bar-Moshe S, et al. 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. Urol Ann. 2011;3(3):119-26doi: 10.4103/0974-7796.84954.
Alkhateeb, S. S., Neill, M., Bar-Moshe, S., Rhijn, B. V., Kakiashvili, D. M., Fleshner, N., Jewett, M., Petein, M., Schulman, C., Hanna, S., Bostrom, P. J., Roumeguere, T., Shariat, S. F., Rorive, S., & Zlotta, A. R. (2011). 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. Urology annals, 3(3), 119-26. https://doi.org/10.4103/0974-7796.84954
Alkhateeb, Sultan S, et al. "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." Urology annals vol. 3,3 (2011): 119-26. doi: https://doi.org/10.4103/0974-7796.84954
Alkhateeb SS, Neill M, Bar-Moshe S, Rhijn BV, Kakiashvili DM, Fleshner N, Jewett M, Petein M, Schulman C, Hanna S, Bostrom PJ, Roumeguere T, Shariat SF, Rorive S, Zlotta AR. 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. Urol Ann. 2011 Sep;3(3):119-26. doi: 10.4103/0974-7796.84954. PMID: 21976923; PMCID: PMC3183702.
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Urol Ann. 2011 Sep;3(3):119-26. doi: 10.4103/0974-7796.84954.

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.

Urology annals

Sultan S Alkhateeb, Mischel Neill, Sas Bar-Moshe, Bas Van Rhijn, David M Kakiashvili, Neil Fleshner, Michael Jewett, Michel Petein, Claude Schulman, Sally Hanna, Peter J Bostrom, Thierry Roumeguere, Shahrokh F Shariat, Sandrine Rorive, Alexandre R Zlotta

Affiliations

  1. Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Canada.

PMID: 21976923 PMCID: PMC3183702 DOI: 10.4103/0974-7796.84954

Abstract

BACKGROUND AND OBJECTIVES: 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.

MATERIALS AND 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).

CONCLUSION: 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.

Keywords: BCG; Bcl-2; EORTC; bladder cancer; cyclinD1; high risk; long-term response; metallothionein 9; p21; p53; waf1/cip

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