title: Intravesical Bacillus Calmette-Guérin Versus Combination of Epirubicin and Interferon-α2a in Reducing Recurrence of Non-Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study.
abstract: Patients with non-muscle-invasive bladder cancer (NMIBC) belonging to the intermediate-risk group should be treated with intravesical instillations to prevent recurrence and progression.
  
  
  
  We compared the outcome of a monthly maintenance bacillus Calmette-Guérin (BCG) regimen with that of epirubicin (EPI) and interferon-α2a (IFN) in patients with NMIBC.
  
  
  
  Our prospective randomized multicenter study comprised 229 eligible patients with frequently recurrent TaT1 grade 1-2 or low-grade NMIBC enrolled between 1997 and 2008.
  
  
  
  The four-arm study involved a single perioperative instillation of EPI plus five weekly instillations of BCG or EPI/IFN, followed by 11 monthly instillations in the 1-yr BCG or EPI/IFN maintenance arms, further followed by four additional quarterly instillations in the two 2-yr maintenance arms.
  
  
  
  Time to recurrence, progression, disease-specific survival, and overall mortality were analyzed using the Kaplan-Meier and cumulative incidence analyses plus the Cox and proportional subdistribution hazards models.
  
  
  
  The median follow-up time was 7.5 and 7.4 yr in the BCG and EPI/IFN groups, respectively. The probability of recurrence was significantly lower in the BCG group than in the EPI/IFN group. The probability was 39% versus 72% at 7.4 yr, respectively (hazard ratio [HR]: 0.41; 95% confidence interval [CI], 0.28-0.60; p<0.001). There was no significant difference in the probability of progression or in overall survival. However, there was a significant difference in disease-specific mortality in favor of the BCG group (HR: 0.20; 95% CI, 0.04-0.91; p=0.04).
  
  
  
  The monthly maintenance BCG regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of EPI/IFN-α2a.
  
  
  
  A monthly bacillus Calmette-Guérin (BCG) regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of epirubicin and interferon-α2a.
  
  
  
  Registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1997, before the current requirements concerning study registrations were implemented.
authors.affiliation: Department of Urology, Seinäjoki Central Hospital, Seinäjoki, Finland. Electronic address: timo.marttila@epshp.fi.
authors.forename: Timo
authors.initials: T
authors.lastname: Marttila
authors.affiliation: Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Järvinen
authors.affiliation: Department of Surgery, Mikkeli Central Hospital, Mikkeli, Finland.
authors.forename: Tapani
authors.initials: T
authors.lastname: Liukkonen
authors.affiliation: Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Erkki
authors.initials: E
authors.lastname: Rintala
authors.affiliation: Department of Urology, Turku University Hospital, Turku, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Boström
authors.affiliation: Department of Surgery, Satakunta Central Hospital, Pori, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Seppänen
authors.affiliation: Department of Urology, Tampere University Hospital, Tampere, Finland.
authors.forename: Teuvo
authors.initials: T
authors.lastname: Tammela
authors.affiliation: Department of Urology, Oulu University Hospital, Oulu, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Hellström
authors.affiliation: Department of Urology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Aaltomaa
authors.affiliation: Department of Urology, Seinäjoki Central Hospital, Seinäjoki, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Leskinen
authors.affiliation: Department of Urology, Seinäjoki Central Hospital, Seinäjoki, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Raitanen
authors.affiliation: Department of Surgery, Hyvinkää Hospital and Helsinki University Hospital, Hyvinkää, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Kaasinen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000283:Administration, Intravesical; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D001500:BCG Vaccine / Q000008:administration & dosage*; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015251:Epirubicin
keywords: Bacillus Calmette-Guérin; Epirubicin; Instillation therapy; Interferon α-2b; Mitomycin C; Recurrent non–muscle-invasive bladder cancer; SWOG