title: Impact of 2004 ISUP/WHO classification on bladder cancer grading.
abstract: OBJECTIVE
  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.
authors.affiliation: Honors Program in Medical Education, University of Miami, Coral Gables, FL, 33124, USA. s.lokeshwar@umiami.edu.
authors.forename: Soum D
authors.initials: SD
authors.lastname: Lokeshwar
authors.affiliation: Department of Pathology, University of Miami, Miller School of Medicine, 1400 NW 12th Ave, Miami, FL, 33136, USA. rruizcordero@med.miami.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ruiz-Cordero
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. marie.ch.hupe@googlemail.com.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hupe
authors.affiliation: Department of Pathology, University of Miami, Miller School of Medicine, 1400 NW 12th Ave, Miami, FL, 33136, USA. mjorda@med.miami.edu.
authors.forename: Merce
authors.initials: M
authors.lastname: Jorda
authors.affiliation: Urology Oncology, Hollywood Memorial Hospital, 9601 Collins Ave, Bal Harbour, FL, 33154, USA. mssoloway@yahoo.com.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Soloway
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010338:Pathology, Clinical; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012955:Societies, Medical; D001749:Urinary Bladder Neoplasms / Q000145:classification* / Q000473:pathology*
keywords: 1998 WHO/ISUP grading; 2004 WHO grading; Bladder cancer; Progression
references.citation: Minerva Med. 2013 Jun;104(3):273-86
references.pmid: 23748281
references.citation: Am J Surg Pathol. 1998 Dec;22(12):1435-48
references.pmid: 9850170
references.citation: Acta Chir Scand. 1965 Oct;130(4):371-8
references.pmid: 5842510
references.citation: BJU Int. 2011 Feb;107(3):404-8
references.pmid: 20707791
references.citation: Am J Clin Pathol. 2004 May;121(5):679-87
references.pmid: 15151208
references.citation: Eur Urol. 2013 Jan;63(1):36-44
references.pmid: 22981672
references.citation: J Clin Pathol. 2010 Oct;63(10):910-5
references.pmid: 20876324
references.citation: Hum Pathol. 1999 Jul;30(7):879-80
references.pmid: 10414511
references.citation: Urology. 2013 Jun;81(6):1123-30
references.pmid: 23522296
references.citation: Eur Urol. 2010 Jun;57(6):1052-7
references.pmid: 19765886
references.citation: PLoS One. 2012;7(10):e47199
references.pmid: 23082147
references.citation: Arch Pathol Lab Med. 2010 Aug;134(8):1160-3
references.pmid: 20670136
references.citation: BJU Int. 2013 Jul;112(1):13-25
references.pmid: 23356411
references.citation: BJU Int. 2008 Jul;102(2):194-7
references.pmid: 18435811
references.citation: Expert Rev Anticancer Ther. 2012 Jan;12(1):87-98
references.pmid: 22149435
references.citation: Urology. 2010 Sep;76(3):593-9
references.pmid: 20381131
references.citation: Eur Urol. 2013 Jan;63(1):45-57
references.pmid: 22917985
references.citation: BJU Int. 2013 Aug;112(3):288-97
references.pmid: 23517232
references.citation: Eur Urol. 2013 Jan;63(1):16-35
references.pmid: 23083804
references.citation: J Urol. 2003 Aug;170(2 Pt 1):438-41
references.pmid: 12853794
references.citation: J Urol. 2007 Oct;178(4 Pt 1):1196-200; discussion 1200
references.pmid: 17698105
references.citation: World J Urol. 2011 Feb;29(1):59-71
references.pmid: 21113783
references.citation: Eur Urol. 2013 Jan;63(1):4-15
references.pmid: 23083902
references.citation: Urol Int. 2007;78(4):338-44
references.pmid: 17495493
references.citation: BMC Med. 2013 Jan 17;11:13
references.pmid: 23327481
references.citation: Eur Urol. 2010 May;57(5):850-8
references.pmid: 19346063
references.citation: J Urol. 2011 Dec;186(6):2194-9
references.pmid: 22019037
references.citation: Cancer. 1987 Dec 1;60(11):2766-74
references.pmid: 3677010
references.citation: Pathol Int. 2010 Jan;60(1):1-8
references.pmid: 20055945