title: The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity?
abstract: OBJECTIVE
  To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC).
  
  
  METHODS
  A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan-Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality.
  
  
  RESULTS
  Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients.
  
  
  CONCLUSIONS
  While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: M Francesca
authors: MF
authors: Monn
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Hristos Z
authors: HZ
authors: Kaimakliotis
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: K Clint
authors: KC
authors: Cary
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Richard
authors: R
authors: Bihrle
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Jose A
authors: JA
authors: Pedrosa
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Timothy A
authors: TA
authors: Masterson
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Richard S
authors: RS
authors: Foster
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Thomas A
authors: TA
authors: Gardner
authors: Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Liang
authors: L
authors: Cheng
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Michael O
authors: MO
authors: Koch
mesh_terms: D000368:Aged; D015653:Cystectomy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery
keywords: bladder urothelial cancer; radical cystectomy; survival; variant histology