title: Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance.
abstract: BACKGROUND
  The optimal dose and duration of intravesical bacillus Calmette-Guérin (BCG) in the treatment of non-muscle-invasive bladder cancer (NMIBC) are controversial.
  
  
  OBJECTIVE
  To determine if a one-third dose (1/3D) is not inferior to the full dose (FD), if 1 yr of maintenance is not inferior to 3 yr of maintenance, and if 1/3D and 1 yr of maintenance are associated with less toxicity.
  
  
  METHODS
  After transurethral resection, intermediate- and high-risk NMIBC patients were randomized to one of four BCG groups: 1/3D-1 yr, 1/3D-3 yr, FD-1 yr, and FD-3 yr.
  
  
  METHODS
  The trial was designed as a noninferiority study with the null hypothesis of a 10% decrease in the disease-free rate at 5 yr. Times to events were estimated using cumulative incidence functions and compared using the Cox proportional hazards regression model.
  
  
  CONCLUSIONS
  In an intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr, there were no significant differences in toxicity between 1/3D and FD. The null hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr could not be rejected. We found that 1/3D-1 yr is suboptimal compared with FD-3 yr (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.59-0.94; p=0.01). Intermediate-risk patients treated with FD do not benefit from an additional 2 yr of BCG. In high-risk patients, 3 yr is associated with a reduction in recurrence (HR: 1.61; 95% CI, 1.13-2.30; p=0.009) but only when given at FD. There were no differences in progression or survival.
  
  
  CONCLUSIONS
  There were no differences in toxicity between 1/3D and FD. Intermediate-risk patients should be treated with FD-1 yr. In high-risk patients, FD-3 yr reduces recurrences as compared with FD-1 yr but not progressions or deaths. The benefit of the two additional years of maintenance should be weighed against its added costs and inconvenience.
  
  
  BACKGROUND
  This study was registered at ClinicalTrials.gov, number NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990.
authors.affiliation: Department of Urology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands. j.oddens@jbz.nl
authors.forename: Jorg
authors.initials: J
authors.lastname: Oddens
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brausi
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.forename: Aldo
authors.initials: A
authors.lastname: Bono
authors.forename: Cees
authors.initials: C
authors.lastname: van de Beek
authors.forename: George
authors.initials: G
authors.lastname: van Andel
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoeltl
authors.forename: Levent
authors.initials: L
authors.lastname: Turkeri
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Sandra
authors.initials: S
authors.lastname: Collette
authors.forename: Willem
authors.initials: W
authors.lastname: Oosterlinck
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D002291:Carcinoma, Papillary / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control; D010352:Patient Dropouts; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*
chemical_list: D001500:BCG Vaccine