Reproducibility and prognostic variability of grade and lamina propria invasion in stages Ta, T1 urothelial carcinoma of the bladder

Purpose: We assessed the reproducibility and prognostic variability of grade and lamina propria invasion in stages Ta, T1 urothelial carcinoma of the bladder. Materials and Methods: A total of 130 consecutive stages Ta, T1 urothelial carcinomas routinely diagnosed by 15 pathologists (original diagnosis) were reviewed by 3 independent experienced pathologists using 1999 WHO criteria (diagnoses 1 to 3 and reviewer consensus diagnosis). Interreviewer disagreement cases were blindly reviewed again. Each remaining disagreement case was discussed in a multihead microscope session to attempt to solve remaining disagreements. In cases of continuing disagreement the majority diagnosis on stage and grade was considered the consensus diagnosis. Stage progression at followup, was the dependent variable. Stage progression-free Kaplan-Meier survival curves and hazard ratios of each stage and grade diagnosis were calculated and prognostic variability was determined. Results: There was complete interobserver agreement on stage and grade among reviewers in 80% and 59% of cases, while it was 87.7% and 75.4%, respectively, after the second review. More than 1 grade difference occurred in 1.5% of cases (0% after the second review). The consensus and original diagnoses agreed on stage and grade in 68.5% and 62.3% of cases, respectively. Assignment of individual cases to 1 category of the 1999 WHO classification per reviewer varied considerably. The incidence of cases classified as stage T1 grade 3 by the reviewers was between 12.3% and 18.9% (average 14.1%). Consensus diagnosis grade had the strongest prognostic value (HR 68.8, range 8.9 to 528.0). Of the 63 original diagnoses of stage T1 tumors the consensus diagnosis down staged 35 (55.6%) to Ta and up staged 8 (12.7%) to T2-3. Progression was more common in the 20 consensus diagnosis stage T1 cases (5 or 25%) than in the 55 original diagnosis stage T1 cases (11 or 20%). Original diagnosis stage T1 tumors that were down staged by the consensus diagnosis showed less progression than consensus diagnosis confirmed stage T1 tumors (17% versus 25%). The prognostically worst subgroup (T1 grade 3) also showed considerable prognostic variation among reviewers (28% to 76% at 5 years of followup), in that the consensus diagnosis again had the highest prognostic significance (FIR 3.5, range 1.2 to 10.2). At the end of the study all pathologists expressed that they were regularly uncertain about stage and grade assessment in an individual case in a considerable percent of all cases. Conclusions: Observer prognostic variability in staging and grading is considerable with potentially strong implications for patients. Interobserver variation did not decrease using the new 1999 WHO grading classification.