title: Intravesical chemotherapy plus bacille Calmette-Guérin in non-muscle invasive bladder cancer: a systematic review with meta-analysis.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Non-muscle-invasive bladder cancer has a significant recurrence and progression rate despite transurethral resection. The current standard of care to lower the risk of recurrence and progression is adjuvant BCG followed by maintenance BCG. Despite this, a significant number of patients experience recurrence and progress to invasive cancer. Several randomized trials have studied combination therapy (BCG with chemotherapy) to try to reduce the recurrence and progression rate. We performed a systematic review with meta-analysis and found that adjuvant BCG followed by maintenance therapy is the appropriate standard of care when compared with combination therapy. We conclude that further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.
  
  
  OBJECTIVE
  To determine if the combination of intravesical chemotherapy and maintenance bacille Calmette-Guérin (BCG), used in sequence, is superior to maintenance BCG alone in the treatment of non-muscle-invasive bladder cancer (NMIBC).
  
  
  METHODS
  We searched biomedical literature databases for randomized controlled trials that compared sequential, intravesical chemotherapy added to maintenance BCG with maintenance BCG alone. Studies that did not use maintenance BCG were excluded. The meta-analysis was performed using the fixed effects model.
  
  
  RESULTS
  Four trials were identified, including 801 patients. Adding chemotherapy to maintenance BCG did not result in a significant reduction in recurrence (relative risk [RR] 0.92; 95% confidence interval [CI] 0.79-1.09; P = 0.32) or progression (RR 0.88; 95% CI 0.61-1.27; P = 0.5). The risk of recurrence (RR 0.75; 95% CI 0.61-0.92; P = 0.006) and progression (RR 0.45; 95% CI 0.25-0.81; P = 0.007) were reduced when the single trial that included isolated Tis was excluded. Toxicity was similar for both groups.
  
  
  CONCLUSIONS
  Adjuvant therapy with induction BCG followed by maintenance BCG is the appropriate standard of care for patients with resected NMIBC at high risk of recurrence. Further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: Baerin B
authors.initials: BB
authors.lastname: Houghton
authors.forename: Venu
authors.initials: V
authors.lastname: Chalasani
authors.forename: Dickon
authors.initials: D
authors.lastname: Hayne
authors.forename: Peter
authors.initials: P
authors.lastname: Grimison
authors.forename: Christopher S B
authors.initials: CS
authors.lastname: Brown
authors.forename: Manish I
authors.initials: MI
authors.lastname: Patel
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stockler
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine