Impact of 2004 ISUP/WHO classification on bladder cancer grading
- 415 Downloads
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.
Keywords1998 WHO/ISUP grading 2004 WHO grading Bladder cancer Progression
Conflict of interest
The authors declare that they have no conflict of interest.
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.
- 1.Jordan AM, Weingarten J, Murphy WM (1987) Transitional cell neoplasms of the urinary bladder: can biologic potential be predicted from histologic grading? Cancer 60:2766–2774. Erratum: (1988) Cancer 61:1385Google Scholar
- 2.Kamat AM, Hegarty PK, Gee JR, Clark PE, Svatek RS, Hegarty N, Shariat SF, Xylinas E, Schmitz-Dräger BJ, Lotan Y, Jenkins LC, Droller M, van Rhijn BW, Karakiewicz PI, International Consultation on Urologic Disease-European Association of Urology Consultation on Bladder Cancer 2012 (2013) ICUD-EAU International Consultation on Bladder Cancer 2012: screening, diagnosis, and molecular markers. Eur Urol 63:4–15. doi: 10.1016/j.eururo.2012.09.057 CrossRefPubMedGoogle Scholar
- 4.Amin MB, McKenney JK, Paner GP, Hansel DE, Grignon DJ, Montironi R, Lin O, Jorda M, Jenkins LC, Soloway M, Epstein JI, Reuter VE, International Consultation on Urologic Disease-European Association of Urology Consultation on Bladder Cancer 2012 (2013) ICUD-EAU International Consultation on Bladder Cancer 2012: pathology. Eur Urol 63:16–35. doi: 10.1016/j.eururo.2012.09.063 CrossRefPubMedGoogle Scholar
- 5.Burger M, Oosterlinck W, Konety B, Chang S, Gudjonsson S, Pruthi R, Soloway M, Solsona E, Sved P, Babjuk M, Brausi MA, Cheng C, Comperat E, Dinney C, Otto W, Shah J, Thürof J, Witjes JA, International Consultation on Urologic Disease-European Association of Urology Consultation on Bladder Cancer 2012 (2013) ICUD-EAU International Consultation on Bladder Cancer 2012: non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 63:36–44. doi: 10.1016/j.eururo.2012.08.061 CrossRefPubMedGoogle Scholar
- 6.Gakis G, Efstathiou J, Lerner SP, Cookson MS, Keegan KA, Guru KA, Shipley WU, Heidenreich A, Schoenberg MP, Sagalowsky AI, Soloway MS, Stenzl A, International Consultation on Urologic Disease-European Association of Urology Consultation on Bladder Cancer 2012 (2013) ICUD-EAU International Consultation on Bladder Cancer 2012: radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol 63:45–57. doi: 10.1016/j.eururo.2012.08.009 CrossRefPubMedGoogle Scholar
- 13.Epstein JI, Amin MB, Reuter VR, Mostofi FK (1998) The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol 22:1435–1448CrossRefPubMedGoogle Scholar
- 14.Otto W, Denzinger S, Fritsche HM, Burger M, Wieland WF, Hofstädter F, Hartmann A, Bertz S (2011) The WHO classification of 1973 is more suitable than the WHO classification of 2004 for predicting survival in pT1 urothelial bladder cancer. BJU Int 107:404–408. doi: 10.1111/j.1464-410X.2010.09515.x CrossRefPubMedGoogle Scholar
- 15.Amin MB, Reuter VE, Epstein J, Grignon DJ, Hansel DE, Lin O, McKenney JK, Montironi R, Paner GP, Soloway M, Members of the Pathology of Bladder Cancer Working group (2012) Pathology consensus guidelines by the pathology of bladder cancer work group. In: Soloway MS, Khoury S (eds) Bladder Cancer, 2nd International Consultation on Bladder Cancer, 2nd edn., pp 63–168Google Scholar
- 18.Cao D, Vollmer RT, Luly J, Jain S, Roytman TM, Ferris CW, Hudson MA (2010) Comparison of 2004 and 1973 World Health Organization grading systems and their relationship to pathologic staging for predicting long-term prognosis in patients with urothelial carcinoma. Urology 76:593–599. doi: 10.1016/j.urology.2010.01.032 CrossRefPubMedGoogle Scholar
- 19.May M, Brookman-Amissah S, Roigas J, Hartmann A, Störkel S, Kristiansen G, Gilfrich C, Borchardt R, Hoschke B, Kaufmann O, Guina S (2010) Prognostic accuracy of individual pathologists in noninvasive urinary bladder carcinoma a multicenter study comparing the 1973 and 2004 World Health Organisation Classifications. Eur Urol 57:850–858. doi: 10.1016/j.eururo.2009.03 CrossRefPubMedGoogle Scholar
- 20.Burger M, Denzinger S, Wieland WF, Stief GC, Hartmann A, Zaak D (2008) Does the current World Health Organization classification predict outcome better in patients with noninvasive bladder cancer of early or regular onset? BJU Int 102:194–197. doi: 10.1111/j.1464-410X.2008.07538.x CrossRefPubMedGoogle Scholar
- 22.Miyamoto H, Brimo F, Schultz L, Ye H, Miller JS, Fajardo DA, Lee TK, Epstein JI, Netto GJ (2010) Low-grade papillary urothelial carcinoma of the urinary bladder: a clinicopathologic analysis of a post-World Health Organization/International Society of Urological Pathology classification cohort from a single academic center. Arch Pathol Lab Med 134:1160–1163. doi: 10.1043/2009-0403-OA.1 PubMedGoogle Scholar
- 25.Chen Z, Ding W, Xu K, Tan J, Sun C, Gou Y, Tong S, Xia G, Fang Z, Ding Q (2012) The 1973 WHO Classification is more suitable than the 2004 WHO Classification for predicting prognosis in non-muscle-invasive bladder cancer. PLoS One 7:e47199. doi: 10.1371/journal.pone.0047199 PubMedCentralCrossRefPubMedGoogle Scholar
- 26.Pellucchi F, Freschi M, Ibrahim B, Rocchini L, Maccagnano C, Briganti A, Rigatti P, Montorsi F, Colombo R (2011) Clinical reliability of the 2004 WHO histological classification system compared with the 1973 WHO system for Ta primary bladder tumors. J Urol 186:2194–2199. doi: 10.1016/j.juro.2011.07.070 CrossRefPubMedGoogle Scholar
- 28.van Rhijn BW, van Leenders GJ, Ooms BC, Kirkels WJ, Zlotta AR, Boeve ER, Jöbsis AC, von der Kwast TH (2010) The pathologist’s mean grade is constant and individualizes the prognostic value of bladder cancer grading. Eur Urol 57:1052–1057. doi: 10.1016/j.eururo.2009.09.022 CrossRefPubMedGoogle Scholar