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SIU-WJU Article of the Month – December 2015
Grade Migration in Bladder Cancer - An Unanticipated Effect of the 2004 WHO Grading System
SIU Academy®. Laguna P. 12/08/15; 119200 Topic: Diagnostics
Prof. Pilar Laguna
Prof. Pilar Laguna

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Abstract
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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.
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.
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