title: Sustained prophylactic effect of intravesical bacille Calmette-Guérin for superficial bladder cancer: a smoothed hazard analysis in a randomized prospective study.
abstract: OBJECTIVE
  A previous meta-analysis had revealed that intravesical chemotherapy was effective in reducing the recurrence of superficial bladder cancer only in the early phase, the phase thought to be caused by tumor cell implantation and/or residual tumor cells. To ascertain the sustained prophylactic effect of intravesical bacille Calmette-Guérin (BCG) after transurethral resection of bladder tumor (TURBT), we compared the estimation of the duration of the effect with that of doxorubicin.
  
  
  METHODS
  Eighty eligible patients with superficial bladder cancer (Stage Ta or T1, grade 1 or 2) were included. Patients were randomly allocated into two groups: the BCG group (six weekly instillations of 80 mg BCG [Tokyo 172 strain]) and the doxorubicin group (17 instillations of 20 mg doxorubicin). A comparison between the smoothed hazards of tumor recurrence was performed using a kernel function method.
  
  
  RESULTS
  All 80 patients (40 each in the BCG and doxorubicin groups) were compared. The median follow-up period was 667 days (range 64 to 1607). The risk of recurrence was significantly lower in the BCG group than in the doxorubicin group (P = 0.017, log-rank test). A smoothed hazard curve depicting the reduced risk of recurrence in the BCG group suggested that BCG is not only efficacious in the early phase of recurrence (up to 500 days after TURBT), but also in the late phase, and the latter is thought to include second primary tumors (new tumors).
  
  
  CONCLUSIONS
  BCG instillation may prevent tumor recurrence caused by both tumor cell implantation and second primary tumors.
authors.affiliation: Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Hinotsu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.forename: Shigeo
authors.initials: S
authors.lastname: Isaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanetake
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kubota
authors.forename: Masao
authors.initials: M
authors.lastname: Kuroda
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shinka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tachibana
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000283:Administration, Intravesical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000517:prevention & control*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D004317:Doxorubicin