title: The long-term outcome of treated high-risk nonmuscle-invasive bladder cancer: time to change treatment paradigm?
abstract: BACKGROUND
  The treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single-center series.
  
  
  METHODS
  The authors reviewed all patients with primary, high-risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow-up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log-rank analysis (2-sided; P < .05).
  
  
  RESULTS
  In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%-18.3%) at a median of 17.2 months (interquartile range, 8.9-35.8 months), including 26.5% (95% CI, 22.2%-31.3%) of the 366 patients who had >5 years follow-up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease-specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%-21.9%) at a median of 28 months (interquartile range, 15-45 months), including 28.7% (95% CI, 24.5%-33.3%) of those who had 5 years of follow-up. Disease-specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease-specific mortality were associated with the receipt of bacillus Calmette-Guerin (P > .6).
  
  
  CONCLUSIONS
  Within a program of conservative treatment, progression of high-risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette-Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease.
authors.affiliation: The Academic Urology Unit and Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Francis
authors.initials: F
authors.lastname: Thomas
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Rosario
authors.forename: Naomi
authors.initials: N
authors.lastname: Rubin
authors.forename: John R
authors.initials: JR
authors.lastname: Goepel
authors.forename: Maysam F
authors.initials: MF
authors.lastname: Abbod
authors.forename: James W F
authors.initials: JW
authors.lastname: Catto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use; D015653:Cystectomy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*
chemical_list: D001500:BCG Vaccine