title: Multiple adverse histological features increase the odds of under staging T1 bladder cancer.
abstract: OBJECTIVE
  The clinical under staging of T1 bladder cancer potentially delays therapy and undermines survival. In this study we evaluated clinicopathological features to aid in the identification of patients with clinical T1 bladder cancer at risk for under staging.
  
  
  METHODS
  We identified patients diagnosed with clinical T1 bladder cancer who underwent cystectomy within 4 months. Muscularis propria was present and uninvolved in initial biopsies or patients had a re-staging biopsy with muscle [corrected] present. Under staging was defined as pT2 or greater, N+ or M+ disease at radical cystectomy. A logistic regression multivariable model was used for the risk of under staging. Overall survival was assessed using the Kaplan-Meier method.
  
  
  RESULTS
  Of 95 patients 26 (27%) had under staged disease. Median followup was 24 months. Compared to accurately staged cases under staged cases were more likely to have muscularis mucosae invasion (54% vs 19%, p = 0.001), mixed histology (42% vs 17%, p = 0.02) and urethral involvement (31% vs 10%, p = 0.03). In a multivariable model muscularis mucosae invasion increased the odds of under staging 9-fold (95% CI 1.5-54.5, p = 0.01). The cumulative association of these risk factors increased the odds of under staging 20-fold (95% CI 1.8-217, p = 0.0029). Median overall survival (years) was lower in patients with under staged disease (1.4 vs 10.6, p <0.001), those with muscularis mucosae invasion (2.2 vs 6.5, p = 0.04) and those with urethral involvement (25th percentile 0.8 vs 2.0, p = 0.01).
  
  
  CONCLUSIONS
  Under staging adversely impacts survival. Muscularis mucosae invasion, urethral involvement and mixed histology cumulatively increase the risk of under staging, and may be valuable in counseling patients regarding early, aggressive intervention.
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan, USA. aweizer@umich.edu
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wasco
authors.forename: Rou
authors.initials: R
authors.lastname: Wang
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Lee
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D002295:Carcinoma, Transitional Cell / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D002423:Cause of Death; D015331:Cohort Studies; D016001:Confidence Intervals; D015653:Cystectomy / Q000379:methods / Q000401:mortality; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging / Q000009:adverse effects / Q000379:methods*; D016017:Odds Ratio; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery