BILCAP-study: Should patients with resected biliary tract cancer really receive adjuvant chemotherapy with capecitabine?

Objective According to the 2019 published ASCO guidelines patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy based solely on the results of the BILCAP trial. Aim of this work is to analyze the quality of the BILCAP trial. Methods Design, conduct, statistics and reporting of the study were analyzed according to the Delphi list and the CONSORT checklist. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Results Several shortcomings could be identified in the study regarding design, conduct, statistics and reporting. The BILCAP study is a randomized, controlled, multicenter, phase 3 study which was done across 44 specialist hepatopancreatobiliary centres in the UK. Despite the inclusion of high specialized centres, the number of included patients each year for each center is extremely low. In particular, a total of 447 patients were included by 44 centers over a period of 11 years, meaning that less than 1 patient was included in this study every year by each center. However, the analysis was not adjusted for center which was one of the stratification factors. Follow up treatment for patients who had disease recurrence was not recorded. Randomization procedure is not well described. Minimization technique was adopted for stratification but mode of application is poorly reported and the choice of variables not justified. No blinding was present. Extensive power evaluations after adjusting the number of needed events, due to lower event rates than expected, were not done. For the observed HR = 0.81 with 234 events statistical power is only around 37%. 4 out of 9 items of the Delphi list and 6 out of 35 items of the CONSORT checklist were not properly addressed. According to the Cochrane Risk of Bias Tool (RoB 2) the overall risk-of-bias judgment for the outcome overall survival of the BILCAP study was “some concerns”. Almost all authors declared to have received funds from pharmaceutical companies, so a conflict of interest cannot be excluded. Additionally, the funding agency for this study (Cancer Research UK and Roche) had an advisory role in design and the first author of the BILCAP study was also involved in the generation of the ASCO guideline. Conclusion Based on the results of this study there is not enough evidence for the administration of adjuvant chemotherapy with capecitabine in patients with resected biliary tract cancer.