World Journal of Urology

, Volume 33, Issue 12, pp 1929–1936 | Cite as

Impact of 2004 ISUP/WHO classification on bladder cancer grading

  • Soum D. Lokeshwar
  • Roberto Ruiz-Cordero
  • Marie C. Hupe
  • Merce Jorda
  • Mark S. SolowayEmail author
Original Article



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).


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.


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).


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.


1998 WHO/ISUP grading 2004 WHO grading Bladder cancer Progression 



Bladder cancer


Bacillus Calmette–Guerin


Bladder tumor


High grade


Low grade


Transurethral resection


Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All human studies have been approved by University of Miami’s Institutional Review Board and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Soum D. Lokeshwar
    • 1
  • Roberto Ruiz-Cordero
    • 2
  • Marie C. Hupe
    • 3
  • Merce Jorda
    • 2
  • Mark S. Soloway
    • 4
    Email author
  1. 1.Honors Program in Medical EducationUniversity of MiamiCoral GablesUSA
  2. 2.Department of PathologyUniversity of Miami, Miller School of MedicineMiamiUSA
  3. 3.Department of Urology and Urologic OncologyHannover Medical SchoolHannoverGermany
  4. 4.Urology OncologyHollywood Memorial HospitalBal HarbourUSA

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