title: The impact of histological reclassification during pathology re-review--evidence of a Will Rogers effect in bladder cancer?
abstract: OBJECTIVE
  We investigated the association of histological reclassification during pathology re-review of radical cystectomy specimens with clinicopathological outcomes in patients initially classified with urothelial carcinoma.
  
  
  METHODS
  We identified 1,211 patients initially diagnosed with urothelial carcinoma at radical cystectomy between 1980 and 2005. All pathological specimens were re-reviewed by a urological pathologist. Survival was estimated using the Kaplan-Meier method and compared with the log rank test.
  
  
  RESULTS
  Of 1,211 cases previously recorded as pure urothelial carcinoma 406 (33%) were reclassified as variant histology. The most common variant histologies identified were squamous in 151 patients (37%) and micropapillary in 62 (15%). Variant histology on re-review was associated with a higher rate of extravesical disease (71%) than urothelial carcinoma at initial diagnosis (52%) or pure urothelial carcinoma on re-review (42%, p<0.0001). Median postoperative followup was 11.1 years, during which 976 patients died, including 564 of bladder cancer. Notably, reclassification resulted in significant stratification of 10-year cancer specific survival, which was 50% in patients with pure urothelial carcinoma after re-review, 47% in those with urothelial carcinoma on initial interpretation and 42% in those with variant histology on re-review (p=0.03). Ten-year overall survival in patients with urothelial carcinoma on re-review, urothelial carcinoma at initial interpretation and variant histology on re-review was 29%, 27% and 24%, respectively (p=0.04).
  
  
  CONCLUSIONS
  Pathological re-review of radical cystectomy specimens identified variant histology in a third of patients. These variants are associated with a high rate of locally advanced disease, which may impact the noted rates of cancer specific and overall survival. Thus, it is critical to be aware of re-review status when interpreting outcomes from historical data sets and stratifying risk.
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Linder
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.forename: William R
authors.initials: WR
authors.lastname: Sukov
authors.forename: Prabin
authors.initials: P
authors.lastname: Thapa
authors.forename: Robert F
authors.initials: RF
authors.lastname: Tarrell
authors.forename: Igor
authors.initials: I
authors.lastname: Frank
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000145:classification* / Q000473:pathology* / Q000601:surgery; D015653:Cystectomy; D005500:Follow-Up Studies; D006801:Humans; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000145:classification* / Q000473:pathology* / Q000601:surgery
keywords: CSS; OS; RC; UC; cancer specific survival; carcinoma; diagnosis; overall survival; pathology; radical cystectomy; urinary bladder; urothelial carcinoma; urothelium