title: Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer.
abstract: BACKGROUND
  Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemoradiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone.
  
  
  METHODS
  In this multicenter, phase 3 trial, we randomly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy. The regimen consisted of fluorouracil (500 mg per square meter of body-surface area per day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C (12 mg per square meter) on day 1. Patients were also randomly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy (in which the volume of bladder receiving full-dose radiotherapy was reduced) in a partial 2-by-2 factorial design (results not reported here). The primary end point was survival free of locoregional disease. Secondary end points included overall survival and toxic effects.
  
  
  RESULTS
  At 2 years, rates of locoregional disease-free survival were 67% (95% confidence interval [CI], 59 to 74) in the chemoradiotherapy group and 54% (95% CI, 46 to 62) in the radiotherapy group. With a median follow-up of 69.9 months, the hazard ratio in the chemoradiotherapy group was 0.68 (95% CI, 0.48 to 0.96; P=0.03). Five-year rates of overall survival were 48% (95% CI, 40 to 55) in the chemoradiotherapy group and 35% (95% CI, 28 to 43) in the radiotherapy group (hazard ratio, 0.82; 95% CI, 0.63 to 1.09; P=0.16). Grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group during treatment (36.0% vs. 27.5%, P=0.07) but not during follow-up (8.3% vs. 15.7%, P=0.07).
  
  
  CONCLUSIONS
  Synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer, as compared with radiotherapy alone, with no significant increase in adverse events. (Funded by Cancer Research U.K.; BC2001 Current Controlled Trials number, ISRCTN68324339.).
authors.affiliation: University of Birmingham, School of Cancer Sciences, Edgbaston, Birmingham B15 2TT, United Kingdom. n.d.james@bham.ac.uk
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: James
authors.forename: Syed A
authors.initials: SA
authors.lastname: Hussain
authors.forename: Emma
authors.initials: E
authors.lastname: Hall
authors.forename: Peter
authors.initials: P
authors.lastname: Jenkins
authors.forename: Jean
authors.initials: J
authors.lastname: Tremlett
authors.forename: Christine
authors.initials: C
authors.lastname: Rawlings
authors.forename: Malcolm
authors.initials: M
authors.lastname: Crundwell
authors.forename: Bruce
authors.initials: B
authors.lastname: Sizer
authors.forename: Thiagarajan
authors.initials: T
authors.lastname: Sreenivasan
authors.forename: Carey
authors.initials: C
authors.lastname: Hendron
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lewis
authors.forename: Rachel
authors.initials: R
authors.lastname: Waters
authors.forename: Robert A
authors.initials: RA
authors.lastname: Huddart
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000009:adverse effects; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009361:Neoplasm Invasiveness; D011878:Radiotherapy / Q000009:adverse effects; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*
chemical_list: D016685:Mitomycin; D005472:Fluorouracil