Background: The European Organization for Research and Treatment of Cancer (EORTC) risk scores are not validated in an independent patient population. Molecular grade (mG) based on fibroblast growth factor receptor 3 (FGFR3) gene mutation status and MIB-1 expression was proposed as an alternative to pathologic grade in bladder cancer (BCa) [1]. Objective: To validate the EORTC risk score and to determine its relation to mG in a series with long-term follow-up as well as to determine reproducibility of pathologic grade and mG. Design, setting, and participants: In this multicenter study, we included 230 patients with primary non-muscle-invasive BCa (NMIBC). Measurements: Four uropathologists reviewed the slides. FGFR3 mutation status was examined by two assays. MIB-1 was assessed by immunohistochemistry. The EORTC risk scores for recurrence and progression were determined. Multivariable analyses were used to find prognostic factors. Results and limitations: Median follow-up was 8.62 yr (interquartile range: 6.6-11.8). FGFR3 mutations were significantly related to favorable disease parameters, whereas altered MIB-1 was frequently seen with pT1, high grade, and high EORTC risk scores. EORTC risk scores were significant in multivariable analyses for recurrence and progression. In multivariable analyses for progression and disease-specific survival, the mG had independent significance. The addition of mG to the multivariable model for progression increased the predictive accuracy from 74.9% to 81.7% (p < 0.001; Mantel-Haenszel test). The mG (89%) was more reproducible than the pathologic grade (41-74%). Conclusions: We validated the EORTC risk scores for primary NMIBC in a clinical and biomarker setting. Next to EORTC risk score, mG proved highly reproducible and predictive. Our long-term results justify an independent prospective analysis of mG and EORTC risk scores.

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Keywords Bladder cancer, EORTC, FGFR3, Grade, MIB-1, Molecular marker, Observer-variability, Progression, Recurrence, Survival, article, bladder cancer, cancer grading, cancer growth, cancer recurrence, cancer risk, cancer survival, clinical assessment, disease free interval, disease free survival, european organization for research and treatment of cancer, female, fibroblast growth factor receptor 3, follow up, gene mutation, human, immunohistochemistry, major clinical study, male, molecular marker, monoclonal antibody Ki 67, multicenter study, non muscle invasive bladder cancer, predictive validity, priority journal, reproducibility, scoring system
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Journal European Urology : Official Journal of the European Association of Urology
van Rhijn, B.W.G, Zuiverloon, T.C.M, Vis, A.N, Radvanyi, F, Leenders, G.J.H.L, Ooms, B.C.M, … Lockwood, G.A. (2010). Molecular grade (FGFR3/MIB-1) and EORTC risk scores are predictive in primary non-muscle-invasive bladder cancer. European Urology : Official Journal of the European Association of Urology, 58(3), 433–441. doi:10.1016/j.eururo.2010.05.043