Volume 58, Issue 3, Pages 433-441 (September 2010) Molecular Grade (FGFR3/MIB-1) and EORTC Risk Scores Are Predictive in Primary Non–Muscle-Invasive Bladder Cancer  Bas W.G. van Rhijn, Tahlita C.M. Zuiverloon, André N. Vis, François Radvanyi, Geert J.L.H. van Leenders, Bert C.M. Ooms, Wim J. Kirkels, Gina A. Lockwood, Egbert R. Boevé, Adriaan C. Jöbsis, Ellen C. Zwarthoff, Theo H. van der Kwast  European Urology  Volume 58, Issue 3, Pages 433-441 (September 2010) DOI: 10.1016/j.eururo.2010.05.043 Copyright © 2010 European Association of Urology Terms and Conditions

Fig. 1 (A) Kaplan-Meier plot for recurrence-free interval for the European Organization for Research and Treatment of Cancer (EORTC) risk score for recurrence based on a weighted score of the variables: grade (World Health Organization 1973), stage, carcinoma in situ, multiplicity, size, and prior recurrence rate [2]. This risk calculator is available online (www.eortc.be/tools/bladdercalculator). The European Association of Urology subsequently adopted this system in its guidelines and, based on these scores, defined patients at low, intermediate, and high risk for recurrence [3]. Our patients had all primary bladder cancer; therefore, prior recurrence rate scored 0 points in all. P(log-rank) was 0.005. (B) Kaplan-Meier plot for progression-free interval of molecular grade (mG), which was based on these parameters: mG1: mutated fibroblast growth factor receptor 3 (FGFR3), low MIB-1; mG2: mutated FGFR3, high MIB-1, and wild-type FGFR3, low MIB-1; mG3: wild-type FGFR3, high MIB-1. Note that the combinations mutated/high and wild-type/low behaved similarly and formed mG2. P(log-rank) was <0.001. (C) Kaplan-Meier plot for progression-free interval of the EORTC risk score for progression based on a weighted score of the six variables listed above. Based on these scores, patients score low, intermediate or high risk for progression [3]. Our patients had all primary bladder cancer; therefore, prior recurrence rate scored 0 points in all. P(log-rank) was <0.001. (D) Kaplan-Meier plot for disease-specific survival of mG (see Fig. 1b for further explanation of mG). P(log-rank) was <0.001. O=observed number of events. European Urology 2010 58, 433-441DOI: (10.1016/j.eururo.2010.05.043) Copyright © 2010 European Association of Urology Terms and Conditions

Fig. 2 Kaplan-Meier plots for progression-free interval of molecular grade (mG) per European Organization for Research and Treatment of Cancer (EORTC) risk category. The combination of the EORTC risk score [2,3] and mG (mG1–3) [1] led to improved prediction of progression. In the intermediate- and high-risk EORTC groups, mG3 was associated with a 2.5-times higher risk of progression compared to mG1–2. A patient with a high-risk EORTC score accompanied by mG3 had a 50% chance of progressing to muscle-invasive and/or metastatic disease (see Fig. 1 for explanations of mG and EORTC risk score for progression.) (A) MG did not enhance prediction of progression in low-risk EORTC scores (p[log-rank]=0.325). Please note that only four patients with primary low-risk EORTC score progressed. (B) MG significantly enhanced prediction of progression in intermediate-risk EORTC scores (p[log-rank]=0.014). (C) MG significantly enhanced prediction of progression in high-risk EORTC scores (p[log-rank]=0.048). O=observed number of events. European Urology 2010 58, 433-441DOI: (10.1016/j.eururo.2010.05.043) Copyright © 2010 European Association of Urology Terms and Conditions