title: The role of adjuvant combination chemotherapy after cystectomy in locally advanced bladder cancer: what we do not know and why.
abstract: BACKGROUND
  Radical cystectomy is the standard treatment for patients with muscle invasive bladder cancer. Three to four cycles of adjuvant chemotherapy is widely used in patients with pT3-pT4a and/or pN+ M0 disease in an effort to delay recurrence and prolong survival. Although a number of clinical trials have been carried out, this paper questions whether the use of adjuvant combination chemotherapy is actually justified.
  
  
  METHODS
  A review of published randomized trials of adjuvant cisplatin-containing combination chemotherapy in locally advanced bladder cancer was undertaken. Four trials including a total of 278 randomized patients were identified.
  
  
  RESULTS
  Although these trials appear to show a significant difference in favor of adjuvant chemotherapy, serious methodological flaws were found. They have major deficiencies in terms of sample size, early stopping of patient entry, statistical analyses, reporting of results and drawing conclusions.
  
  
  CONCLUSIONS
  These trials provide insufficient evidence to support the routine use of adjuvant chemotherapy in clinical practice due to small sample sizes, confusing analyses and terminology, and the reporting of questionable conclusions. Analyses of the duration of survival were either not done or were inconclusive and quality of life has not been considered. New large scale, multicenter trials are imperative in order to provide convincing results.
authors.affiliation: EORTC Data Center, Brussels, Belgium. rsy@eortc.be
authors.forename: R
authors.initials: R
authors.lastname: Sylvester
authors.forename: C
authors.initials: C
authors.lastname: Sternberg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D018572:Disease-Free Survival; D006801:Humans; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D018401:Sample Size; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery