title: Treatment of patients with superficial bladder cancer stratified by risk groups treated with lyophilized Moreau-Rio de Janeiro BCG strain.
abstract: BACKGROUND
  The Moreau-Rio de Janeiro BCG strain is considered the most effective to stimulate immunologic activity in mice. The objective of this prospective study was to evaluate BCG results for patients with superficial bladder cancer stratified by risk groups.
  
  
  METHODS
  From April 1988 to May 2000, 100 patients were treated by transurethral resection for bladder tumor, followed by intravesical instillation of 40 mg BCG, with induction and maintenance cycles. Fisher exact test and Chi-square test, with 95% significance, were used to evaluate possible associations among variables. The Kaplan-Meier method was used to evaluate the disease-free interval and patients' survival, while log-rank test was used to compare the curves among the groups.
  
  
  RESULTS
  The median follow-up was 69.3 months and varied from 10 to 153 months. Overall recurrence and progression rates were 55% and 13%, respectively. The medium time to recurrence was 9.4 months and to progression was 24.4 months. The cancer specific survive was 90%. Univariate analysis revealed that tumor recurrence was significantly associated with weekly BCG failure (p=0.011), multifocality (p=0.001), number of recurrences after primary therapy (p=0.001) and the need to Mitomycin C instillation (p=0.001). However, no variable was significantly associated with recurrence in multivariate analysis. There were significant associations, in univariate analysis, between disease progression and the following variables: tumor grade, weekly and 15-days BCG failure, both as first line and second line therapy, recurrence and need of Mitomycin C therapy. Independent variables to progression were 6.7 relative risk to weekly BCG failure, tumor grade and 15-days BCG (p= 0.08; CI=0.79-56.7), 2.4 (p= 0.11; CI=0.80-7.15) and 1.5 (p=0.23; CI=1.05-2.13), respectively. Patient stratification by risk groups were able to predict progression (p=0.045), but not recurrence (p=0.311). Disease progression rates were 3.2%, 12.2% e 25%, in low, intermediate and high risk groups, respectively. The BCG administration was well tolerated, and 21 patients (21%) didn't present any side effects.
  
  
  CONCLUSIONS
  Intravesical instillation of BCG was overall well tolerated. Adjuvant BCG didn't decrease significantly recurrence rates, and 16% of the patients underwent alternative therapy with intravesical Mitomycin to prevent new recurrences. The risk group classification was able to select patients with high risk to progression. Tumor grade, BCG failure as first and second line therapies, were predictive factors of poor prognosis. BCG of Moreau-Rio de Janeiro strain was well tolerated, similar to other strains used in literature.
authors.affiliation: Section of Urology, Department of Pelvic Surgery, Cancer Hospital, São Paulo, SP, Brazil.
authors.forename: Francisco P
authors.initials: FP
authors.lastname: Fonseca
authors.forename: Wilson
authors.initials: W
authors.lastname: Bachega
authors.forename: Stênio C
authors.initials: SC
authors.lastname: Zequi
authors.forename: Alvaro S
authors.initials: AS
authors.lastname: Sarkis
authors.forename: Gustavo
authors.initials: G
authors.lastname: Guimaraes
authors.forename: Antonio V M
authors.initials: AV
authors.lastname: Priante
authors.forename: Ademar
authors.initials: A
authors.lastname: Lopes