title: A meta-analysis of randomised trials suggests a survival benefit for combined radiotherapy and radical cystectomy compared with radical radiotherapy for invasive bladder cancer: are these data relevant to modern practice?
abstract: OBJECTIVE
  Treatment options for muscle-invasive bladder cancer include radical cystectomy or radical radiotherapy, and the prevailing choice varies by country. The ideal treatment would be a bladder-preserving therapy without compromising survival. The objective of this review was to compare the overall survival after radical surgery (cystectomy) with radical radiotherapy in patients with muscle-invasive cancer.
  
  
  METHODS
  We searched the Cochrane Controlled Trials Register, Medline, EMBASE, Cancerlit, Healthstar and the Database of Abstracts of Reviews of Effectiveness. Authors of unpublished data were contacted. Randomised trials comparing surgery (alone or with preoperative radiotherapy) with radiotherapy were eligible for assessment. Three reviewers assessed trial quality based on the Cochrane Guidelines. Data were extracted from the text of the article or extrapolated from the Kaplan-Meier plot. The Peto odds ratio was determined to compare the overall survival and disease-specific survival. Analysis was performed on an intention-to-treat basis and treatment actually received.
  
  
  RESULTS
  No randomised trials comparing surgery alone with radiotherapy alone were identified. Three randomised trials comparing preoperative radiotherapy followed by radical cystectomy (surgery) versus radical radiotherapy with salvage cystectomy (radical radiotherapy) were eligible for assessment. These trials represented a total of 439 patients, 221 randomised to surgery and 218 to radical radiotherapy. Three trials were combined for the overall survival results, and one was evaluable for the disease-specific survival analysis. The mean overall survival (intention-to-treat analysis) at 3 and 5 years were 45% and 36% for surgery, and 28% and 20% for radiotherapy, respectively. Peto odds ratio (95% confidence interval [CI]) analysis consistently favoured surgery in terms of overall survival. The results were significantly in favour of surgery at 3 years (OR = 1.91, 95% CI 1.30-2.82) and at 5 years (OR = 1.85, 95% CI 1.22 -2.82). On a treatment-received basis, the results were significantly in favour of surgery at 3 years (OR 1.84, 95% CI 1.17-2.90) and 5 years (OR 2.17, 95% CI 1.39-3.38) for overall survival, and at 3 years (OR 1.96, 95% CI 1.06-3.65) for disease-specific survival.
  
  
  CONCLUSIONS
  The analysis of this review suggests that there is an overall survival benefit with combined preoperative radiotherapy plus radical surgery compared with radical radiotherapy plus salvage cystectomy in patients with muscle-invasive bladder cancer. However, it must be considered that only three trials were included for analysis, the patient numbers were small and that many patients did not receive the treatment they were randomised to. It must also be noted that many improvements in radiotherapy and surgery have taken place since the initiation of these trials; therefore, the data may not be readily extrapolated to modern practice. Ideally, a new trial comparing modern bladder-sparing therapy with the latest surgical approach to this disease is required.
authors.affiliation: Cochrane Prostatic Diseases and Urological Cancers Group, Cochrane Unit, Velindre NHS Trust, Cardiff, UK. shelley@velindre-tr.wales.nhs.uk
authors.forename: M D
authors.initials: MD
authors.lastname: Shelley
authors.forename: T J
authors.initials: TJ
authors.lastname: Wilt
authors.forename: J
authors.initials: J
authors.lastname: Barber
authors.forename: M D
authors.initials: MD
authors.lastname: Mason
mesh_terms: D015653:Cystectomy; D019317:Evidence-Based Medicine; D006801:Humans; D018482:Muscle, Skeletal / Q000473:pathology; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012042:Registries / Q000706:statistics & numerical data*; D016879:Salvage Therapy; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*