title: Randomized noninferiority trial of reduced high-dose volume versus standard volume radiation therapy for muscle-invasive bladder cancer: results of the BC2001 trial (CRUK/01/004).
abstract: OBJECTIVE
  To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer.
  
  
  METHODS
  In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years).
  
  
  RESULTS
  Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT - sRT) was 6.4% (95% confidence interval -7.3%, 16.8%) under an intention to treat analysis and 2.6% (-12.8%, 14.6%) in the "per-protocol" population.
  
  
  CONCLUSIONS
  In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.
authors: Institute of Cancer Research. robert.huddart@icr.ac.uk
authors: Robert A
authors: RA
authors: Huddart
authors: Emma
authors: E
authors: Hall
authors: Syed A
authors: SA
authors: Hussain
authors: Peter
authors: P
authors: Jenkins
authors: Christine
authors: C
authors: Rawlings
authors: Jean
authors: J
authors: Tremlett
authors: Malcolm
authors: M
authors: Crundwell
authors: Fawzi A
authors: FA
authors: Adab
authors: Denise
authors: D
authors: Sheehan
authors: Isabel
authors: I
authors: Syndikus
authors: Carey
authors: C
authors: Hendron
authors: Rebecca
authors: R
authors: Lewis
authors: Rachel
authors: R
authors: Waters
authors: Nicholas D
authors: ND
authors: James
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D016001:Confidence Intervals; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D011832:Radiation Injuries / Q000473:pathology; D011879:Radiotherapy Dosage; D018401:Sample Size; D006113:United Kingdom; D001743:Urinary Bladder / Q000473:pathology / Q000528:radiation effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D016685:Mitomycin; D005472:Fluorouracil
references: J Urol. 1989 Dec;142(6):1448-53; discussion 1453-4
references: 2585617
references: Radiother Oncol. 1986 Dec;7(4):299-310
references: 3101140
references: J Clin Oncol. 2001 Feb 1;19(3):666-75
references: 11157016
references: Cancer. 1997 Nov 1;80(9):1803-4
references: 9351551
references: Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22
references: 2032882
references: J Clin Oncol. 2009 Sep 1;27(25):4055-61
references: 19636019
references: Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):197-207
references: 15093917
references: Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):e457-62
references: 21945107
references: N Engl J Med. 2012 Apr 19;366(16):1477-88
references: 22512481
references: J Clin Oncol. 2002 Jul 15;20(14):3061-71
references: 12118019
references: Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1041-2
references: 7713774
references: Eur Urol. 2012 Apr;61(4):705-11
references: 22101114
references: Int J Radiat Oncol Biol Phys. 1989 Feb;16(2):369-71
references: 2921141
references: Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6
references: 7713792
references: Eur Urol. 2000 Sep;38(3):279-86
references: 10940701
references: Clin Oncol (R Coll Radiol). 2006 Aug;18(6):466-73
references: 16909970
references: Clin Oncol (R Coll Radiol). 2009 Jun;21(5):380-4
references: 19394804
references: Ann Oncol. 2001 Jul;12(7):929-35
references: 11521797