Adjuvant chemotherapy improves oncological outcomes of resectable intrahepatic cholangiocarcinoma A meta-analysis

Objective: To define the role of adjuvant chemotherapy in the management of resectable intrahepatic cholangiocarcinoma (ICC) by performing a meta-analysis. Summary background data: Oncological benefit of adjuvant chemotherapy in resectable ICC remains controversial, high-level evidence in such context is lacking. Method: A comprehensive search using Pubmed, EMbase, and Web of Science was performed from inception to October 2018. Studies compared the survival of patients receiving adjuvant chemotherapy versus surgery alone were included. Data were analyzed using random effect model. Quality of each study and presence of publication bias were assessed by Newcastle-Ottawa score (NOS) and funnel plot with Egger test respectively. Results: The present meta-analysis included 15 studies (all were retrospective series) and 5060 patients. Adjuvant chemotherapy was administered either intravenously or intra-arterially in the form of trans-arterial chemo-embolization (TACE). The average NOS for the included studies was 6.5. Pooled analysis of the included studies demonstrated significant advantage in the adjuvant chemotherapy group (HR 0.66, 0.55-079, P <.001, I-square [I-2] = 20.8%). After 2 studies were removed for heterogeneity, advantage of adjuvant chemotherapy remained (HR 0.72, 0.62-0.84, P <.001, I-2 = 0%). Funnel plot suggested no significant publication bias (Egger test, 2-tailed P = .203). Subgroup analyses suggested that intravenous route of chemotherapy injection (P <.001) and use of gemcitabine base regimen (P = .004) are associated with improved overall survival. Adjuvant chemotherapy did not improve disease-free survival in subgroup analysis (P = .94). Conclusion: Adjuvant chemotherapy is associated with improved overall survival and should be considered in patients with ICC following curative resection and in particular to patients with advance disease.