Impact of 2004 ISUP/WHO classification on bladder cancer grading

Purpose: To determine whether implementation of the 2004 WHO/ISUP bladder cancer (BCa) grading system caused a grade migration, i.e., more tumors being graded as high grade (HG). Methods: Data on 1040 BCa cases from 668 patients treated at our institution between 2000 and 2013 and reviewed by six pathologists were evaluated: low grade (LG): 249; HG: 791; Ta: 389; T1: 214; CIS: 95; ≥T2: 342. Differences in LG or HG cases (expressed as %BCa cases/year) were analyzed by Mann–Whitney test. Correlation between the year of diagnosis and clinical/pathological parameters was evaluated by logistic regression analyses. Results: During the study period, BCa cases diagnosed as LG significantly decreased with a corresponding increase in HG cases. Nonlinear regression analysis indicated that ~2008 was the crossover point for grade migration; %LG: 31.8 ± 4.8 (2000–2007); 14.1 ± 7.0 (2008–2013); %HG: 68.2 ± 4.8 (2000–2007); 85.9 ± 6.9 (2008–2013), P = 0.004. The grade migration was confined to Ta cases with %LG Ta cases diagnosed decreasing by 3.6-fold from 2000–2007 to 2008–2013 (P = 0.004). Univariate and multivariate analyses confirmed the grade migration following the adoption of the 2004 system (P < 0.0001). Kaplan–Meier curves showed no significant differences between the two time intervals in terms of disease progression (P > 0.05). Conclusions: Implementation of the 2004 WHO/ISUP system caused a significant increase in pathologists grading Ta cases as HG; however, this increase did not seem to correlate with disease progression. Since LG and HG Ta tumors are treated differently, grade migration may impact the clinical management of BCa patients.