Results of BC2001: A 2×2 phase III randomised trial of synchronous chemo-radiotherapy (CRT) compared to radiotherapy (RT) alone and standard (sRT) versus reduced high-dose volume RT (rvRT) in muscle invasive bladder cancer (MIBC) (CRUK/01/004


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Syed Hussain1, Emma Hall2, Peter Jenkins3, Jean Tremlett4, Christine Rawlings5, Malcolm Crundwell6, Rebecca Lewis2, Carey Hendron1, Rachel Waters2, Robert Huddart2
2The Institute of Cancer Research, Sutton, UK,3Cheltenham General Hospital, UK,4Brighton and Sussex University Hospitals NHS Trust, UK,5South Devon Healthcare NHS Foundation Trust, Torbay, UK,6Royal Devon and Exeter Hospital, UK

Background

BC2001 tests the hypotheses in MIBC that synchronous CRT improves loco-regional control and reducing volume of bladder irradiated to full RT dose reduces late toxicity without detriment to tumour control.

Method

Patients with MIBC were randomised to CRT vs RT alone and/or to sRT (to tumour and whole bladder with 1.5cm margin) vs rvRT (tumour +1.5cm margin: 100(+/-5)% target dose; remaining bladder: 80% target dose). RT was 64Gy/32 fractions (f) in 6.5 weeks or 55Gy/20f in 4 weeks. CRT was mitomycin C 12mg/m2 iv bolus (MMC) day 1 of RT and 5-fluorouracil (5FU) continuous infusion 500mg/m2/24 hours for 10 days in total corresponding to RT f1-5 (week 1) and f16-20 (week 4). Primary endpoint was loco-regional disease-free survival (LRDFS). Secondary endpoints included toxicity, quality of life, salvage cystectomy rate and overall survival (OS)

Results

From August 2001-April 2008, 458 patients were recruited (182 CRT vs 178 RT; 108 sRT vs 111 rvRT).  Median age was 73(IQR 66-78) years.  Overall, 40(13.3%) patients experienced grade 3/4 RTOG post-treatment toxicity: CRT:10(8.3%) vs RT:17(15.9%), p=0.07; sRT:9(11.5%) vs rvRT:13(17.3%), p=0.31.  There was no evidence of difference in LRDFS or OS between sRT and rvRT.  With 49 months median follow-up, LRDFS was improved with CRT (hazard ratio HR=0.66, 95%CI:0.46–0.95; p=0.02).  For OS, HR=0.81(0.60–1.09); p=0.16.  Cystectomy rate was not significantly different between randomised groups (CRT:10.4% vs RT:15.2%, p=0.20; sRT:11.1% vs rvRT:11.7%, p=0.61)

Conclusion

Chemo-radiotherapy significantly improves local control in MIBC with no increase in late toxicity. We believe chemo-radiotherapy should be considered as optimal treatment in conservatively managed patients with MIBC