title: The effect of age on the efficacy of maintenance bacillus Calmette-Guérin relative to maintenance epirubicin in patients with stage Ta T1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911.
abstract: BACKGROUND
  Although maintenance bacillus Calmette-Guérin (BCG) is the recommended treatment in high-risk non-muscle-invasive bladder cancer (NMIBC), its efficacy in older patients is controversial.
  
  
  OBJECTIVE
  To determine the effect of age on prognosis and treatment outcome in patients with stage Ta T1 NMIBC treated with maintenance BCG.
  
  
  METHODS
  A total of 957 patients with intermediate- or high-risk Ta T1 (without carcinoma in situ) NMIBC were randomized in European Organization for Research and Treatment of Cancer (EORTC) trial 30911 comparing six weekly instillations of epirubicin, BCG, and BCG plus isoniazid followed by three weekly maintenance instillations over 3 yr.
  
  
  METHODS
  Cox multivariate proportional hazards regression models were used to assess the relative importance of age for recurrence, progression, overall survival, and NMIBC-specific survival with adjustment for EORTC risk scores.
  
  
  CONCLUSIONS
  Overall, 822 eligible patients were included: 546 patients in the BCG with or without INH arms and 276 in the epirubicin arm. In patients treated with BCG with or without INH, 34.1% were >70 yr of age and 3.7% were >80 yr. With a median follow-up of 9.2 yr, patients >70 yr had a shorter time to progression (p=0.028), overall survival (p<0.001), and NMIBC-specific survival (p=0.049) after adjustment for EORTC risk scores in the multivariate analysis. The time to recurrence was similar compared with the younger patients. BCG was more effective than epirubicin for all four end points considered, and there was no evidence that BCG was any less effective compared with epirubicin in patients >70 yr.
  
  
  CONCLUSIONS
  In intermediate- and high-risk Ta T1 urothelial bladder cancer patients treated with BCG, patients >70 yr of age have a worse long-term prognosis; however, BCG is more effective than epirubicin independent of patient age.
  
  
  RESULTS
  Intravesical bacillus Calmette-Guérin for non-muscle-invasive bladder cancer is less effective in patients >70 yr of age, but it is still more effective than epirubicin.
  
  
  BACKGROUND
  This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC 30911; http://www.cancer.gov/clinicaltrials/search/view?cdrid=77075&version=HealthProfessional&protocolsearchid=12442243#StudyIdInfo_CDR0000077075).
authors.affiliation: Department of Urology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. Electronic address: J.oddens@jbz.nl.
authors.forename: Jorg R
authors.initials: JR
authors.lastname: Oddens
authors.affiliation: Headquarters, European Organization for Research and Treatment of Cancer, Brussels, Belgium.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sylvester
authors.affiliation: Department of Urology, New Estense-S. Agostino Hospital Ausl, Modena, Italy.
authors.forename: Maurizio A
authors.initials: MA
authors.lastname: Brausi
authors.affiliation: Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Kirkels
authors.affiliation: Department of Urology, Academic Hospital, Maastricht, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van de Beek
authors.affiliation: Department of Urology, OLVG, Amsterdam, The Netherlands.
authors.forename: George
authors.initials: G
authors.lastname: van Andel
authors.affiliation: Department of Urology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: de Reijke
authors.affiliation: Department of Urology, St James's University Hospital, Leeds, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Prescott
authors.affiliation: Department of Urology, Radboud University Nijmegen Medical Center, The Netherlands.
authors.forename: J Alfred
authors.initials: JA
authors.lastname: Witjes
authors.affiliation: Department of Urology, Gent University Hospital, Ghent, Belgium.
authors.forename: Willem
authors.initials: W
authors.lastname: Oosterlinck
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy / Q000379:methods; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery
chemical_list: D001500:BCG Vaccine; D015251:Epirubicin
keywords: Age; Bacillus Calmette-Guérin; Epirubicin; Instillation therapy; Non–muscle-invasive bladder cancer