Results of the radiotherapy comparison within BC2001 – a phase III randomised trial of standard versus reduced volume radiotherapy with or without synchronous chemotherapy in muscle invasive bladder cancer


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Robert Huddart1, Emma Hall2, Nicholas James3, Sayed Hussain3, Malcolm Crundwell4, Jean Tremlett5, Peter Jenkins6, Christine Rawlings7, Shaun Rogers2

1The Institute of Cancer Research, Clinical Academic Radiotherapy, Sutton, UK, 2The Institute of Cancer Research, Clincal Trials and Statistics Unit, Sutton, UK, 3University of Birmingham, CR-UK Institute for Cancer Studies, Birmingham, UK, 4Royal Devon and Exeter Hospital NHS Foundation Trust, Department of Urology, Exeter, UK, 5Sussex Cancer Centre, Department of Radiotherapy, Brighton, UK, 6Cheltenham General Hospital, Gloucestershire Oncology Centre, Cheltenham, UK, 7South Devon Healthcare Trust, Department of Radiotherapy, Torquay, UK

Abstract

Background

BC2001 was a multicentre 2x2 factorial trial and investigated whether radiotherapy (RT) volume modification reduces late toxicity without detriment to tumour control and whether concomitant chemotherapy improves loco-regional control in management of muscle invasive bladder cancer.

Method

Patients were randomised to A) RT alone vs RT plus synchronous chemotherapy - 5FU and MMC; and B) RT to the tumour and whole bladder (sRT) with 1.5cm margin vs. reduced volume RT (rvRT) where the tumour +1.5cm margin was treated to 100 +/- 5% target dose and the remaining bladder received 80% target dose. Primary endpoint for the RT comparison was toxicity at 1 year. Secondary endpoints included toxicity during treatment, at 6 and12 months and annually thereafter.

Results

Slow recruitment closed RT comparison in September 2006 with 219 patients accrued. 154 patients (78 sRT; 76 rvRT) were alive and evaluable for late toxicity at 1 year providing approximately 70% power, 2-sided 5% significance to detect a reduction in RTOG G3 or 4 toxicity from 40% to 20%.. Median age was 74 years (IQR 49-87), 83% were male, and 49% had WHO performance 1 or 2. CTC Grade 3/4 acute toxicity was reported in around 1/3 of stRT patients and 1/4 of rvRT patients. G3/4 toxicity at 1 year was reported in 28 pts (19(25%) sRT, 9(12%) rvRT, chi2 p < 0.05).

Conclusion

Late toxicities were less frequent than expected. rvRT may offer improvements in acute and possibly late toxicity, but it is important to establish its effectiveness in tumour control.

Background

BC2001 was a multicentre 2x2 factorial trial and investigated whether radiotherapy (RT) volume modification reduces late toxicity without detriment to tumour control and whether concomitant chemotherapy improves loco-regional control in management of muscle invasive bladder cancer.

Method

Patients were randomised to A) RT alone vs RT plus synchronous chemotherapy - 5FU and MMC; and B) RT to the tumour and whole bladder (sRT) with 1.5cm margin vs. reduced volume RT (rvRT) where the tumour +1.5cm margin was treated to 100 +/- 5% target dose and the remaining bladder received 80% target dose. Primary endpoint for the RT comparison was toxicity at 1 year. Secondary endpoints included toxicity during treatment, at 6 and12 months and annually thereafter.

Results

Slow recruitment closed RT comparison in September 2006 with 219 patients accrued. 154 patients (78 sRT; 76 rvRT) were alive and evaluable for late toxicity at 1 year providing approximately 70% power, 2-sided 5% significance to detect a reduction in RTOG G3 or 4 toxicity from 40% to 20%.. Median age was 74 years (IQR 49-87), 83% were male, and 49% had WHO performance 1 or 2. CTC Grade 3/4 acute toxicity was reported in around 1/3 of stRT patients and 1/4 of rvRT patients. G3/4 toxicity at 1 year was reported in 28 pts (19(25%) sRT, 9(12%) rvRT, chi2 p < 0.05).

Conclusion

Late toxicities were less frequent than expected. rvRT may offer improvements in acute and possibly late toxicity, but it is important to establish its effectiveness in tumour control.