title: Does the extent of variant histology affect oncological outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy?
abstract: BACKGROUND
  To evaluate the effect of variant histology and its extent on oncological outcomes in patients with urothelial carcinoma of the bladder (UCB) who are treated with radical cystectomy.
  
  
  METHODS
  Data from 485 patients with UCB who were treated with radical cystectomy without neoadjuvant chemotherapy at a single academic center between 1996 and 2011 were collected retrospectively. All pathologic specimens were meticulously re-reviewed for the presence and extent of variant UCB histologies. Cox regression models were used to evaluate the association with disease recurrence and cancer-specific survival.
  
  
  RESULTS
  Variant histology was present in 96 patients (19.8%), with squamous cell differentiation (12.6%) being most common. In patients with variant histology, the median and mean extent was 70% and 60%, respectively. Variant histology was associated with female sex, advanced tumor stage, less presence of concomitant carcinoma in situ, and administration of adjuvant chemotherapy (P ≤ 0.001). The presence of variant histology and non-squamous cell differentiation was associated with cancer-specific mortality (pairwise P ≤ 0.02). Moreover, non-squamous cell differentiation was associated with disease recurrence (P = 0.002). The presence of variant histology, non-squamous cell differentiation, and the extent of variant histology were associated with cancer-specific mortality in univariable but not in multivariable analyses.
  
  
  CONCLUSIONS
  The presence of variant histology, particularly non-squamous cell differentiation, and its extent are associated with inferior survival. However, they are not independent predictors of outcomes. The association of variant histology with established predictors of aggressive tumor biology is likely impairing oncological outcomes and thus has to be considered in clinical decision making.
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Soave
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Selina
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Dahlem
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Engel
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Kluth
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lisa-Marie
authors.initials: LM
authors.lastname: John
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Department of Urology, University Medical Center Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: mrink@uke.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
mesh_terms: D000368:Aged; D015653:Cystectomy / Q000379:methods*; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology* / Q000601:surgery*
keywords: Histology; Outcome; Radical cystectomy; Urinary bladder cancer; Urothelial carcinoma