title: Long-term efficacy of maintenance bacillus Calmette-Guérin versus maintenance mitomycin C instillation therapy in frequently recurrent TaT1 tumours without carcinoma in situ: a subgroup analysis of the prospective, randomised FinnBladder I study with a 20-year follow-up.
abstract: BACKGROUND
  The long-term prospective data on bacillus Calmette-Guérin (BCG) and mitomycin C (MMC) instillation therapy are limited.
  
  
  OBJECTIVE
  To compare the long-term benefit of BCG and MMC maintenance therapy in patients with recurrent bladder carcinoma.
  
  
  METHODS
  Eighty-nine patients with frequently recurrent TaT1 disease without carcinoma in situ (CIS) were eligible. Originally, the patients were enrolled in the prospective FinnBladder I study between 1984 and 1987 and randomised to receive BCG or MMC. Both regimens involved five weekly instillations, followed by monthly instillations for 2 yr. Because of alkalinising the urine and adjusting the dose to bladder capacity, the average concentration of MMC was low: 30-40 mg in 150-200 ml of phosphate buffer. Overall median follow-up time was 8.5 yr, whereas the median follow-up time of the patients who were still alive was 19.4 yr.
  
  
  METHODS
  Primary end points were time to first recurrence and overall mortality. Secondary end points were progression and disease-specific mortality.
  
  
  CONCLUSIONS
  Thirty-six of 45 patients (80.0%) in the MMC group experienced recurrence in contrast to 26 of 44 patients (59.1%) in the BCG group. This finding was reflected in significantly lower cumulative incidence estimates in the BCG group (p=0.005). There was a weak trend for fewer progressions (p=0.1) and cancer-specific deaths (p=0.2) in the cumulative incidence analysis, as 4 patients versus 10 patients progressed and 4 patients versus 9 patients died from the disease in the BCG group versus the MMC group, respectively. No difference existed in the overall mortality. The study population, however, was too small for conclusive evidence about progression or survival.
  
  
  CONCLUSIONS
  An intensive intravesical BCG immunotherapy results in a sustained and significant long-term reduction in recurrence in frequently recurrent bladder carcinoma. The relatively low progression rate during the long follow-up suggests that it may be difficult to show significant differences in overall mortality with a substantially larger but otherwise similar study population.
  
  
  BACKGROUND
  Registration was not considered to be necessary at this stage of the follow-up because the study was initiated as early as 1984 and the last randomisation took place in July 1987, that is, long before the current requirements concerning study registrations were implemented.
authors.affiliation: Helsinki University Hospital, Department of Urology, Helsinki, Finland. riikka.jarvinen@hus.fi
authors.forename: Riikka
authors.initials: R
authors.lastname: Järvinen
authors.forename: Eero
authors.initials: E
authors.lastname: Kaasinen
authors.forename: Anna
authors.initials: A
authors.lastname: Sankila
authors.forename: Erkki
authors.initials: E
authors.lastname: Rintala
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage* / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D016685:Mitomycin