title: Reproducibility and prognostic value of WHO1973 and WHO2004 grading systems in TaT1 urothelial carcinoma of the urinary bladder.
abstract: BACKGROUND
  European treatment guidelines of TaT1 urinary bladder urothelial carcinomas depend highly on stage and WHO1973-grade but grading reproducibility is wanting. The newer WHO2004 grading system is still debated and both systems are currently used.
  
  
  OBJECTIVE
  To compare reproducibility and prognostic value (of stage progression) of the WHO1973 and WHO2004.
  
  
  METHODS
  One hundred and ninety-three primary urothelial carcinomas were reviewed. Follow-up data were retrieved from the patient records. Kappa statistics and Harrell's C-index were used.
  
  
  RESULTS
  Median follow-up was 75 months (range 1-127). 17 patients (9%) progressed, 82% of these within and 18% after 60 months. The distribution of WHO73-grades 1, 2 and 3 was 23%, 51% and 26%, interobserver agreement for each individual grade was 66% (kappa = 0.68), while for grades 1&2 versus 3 89% (kappa = 0.68). Intraobserver reproducibility was 68-63% for WHO73 and 88-89% for WHO73 as 1&2 vs.3. Progression free survival rates at 5 years were 95% (grade 1), 98% (grade 2) and 82% (grade 3) and 96% and 82% for grades 1&2 versus 3 (Hazard Ratio, HR, 5.4, p = 0.003). Using WHO2004, 62% were low grade and 38% high grade, inter-observer agreement 87% (kappa = 0.70), intraobserver reproducibility 93%, and progression free 5-year survival rates 97% and 85% (HR 6.6, p = 0.004). Positive and negative predictive values for stage progression within 5 years for the WHO73 (1&2 vs. 3) were 18% and 96%, and 15% and 97% for the WHO04. Using Harrell's C-index, none of the grading systems was prognostically superior.
  
  
  CONCLUSIONS
  None of the grading systems is prognostically stronger than the others. Most importantly, inter-observer reproducibility and sensitivities for stage progression of both systems are low and need improvement for optimal treatment.
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway ; Clinical Institute-1, University of Bergen, Bergen, Norway.
authors.forename: Ok Målfrid
authors.initials: OM
authors.lastname: Mangrud
authors.affiliation: Department of Pathology, Innlandet Hospital Trust, Lillehammer, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Waalen
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway ; Clinical Institute-1, University of Bergen, Bergen, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.affiliation: Department of Research, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Ingvild
authors.initials: I
authors.lastname: Dalen
authors.affiliation: Department of Urology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Ilker
authors.initials: I
authors.lastname: Tasdemir
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway ; Clinical Institute-1, University of Bergen, Bergen, Norway.
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods* / Q000592:standards*; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*