The role of down staging treatment in the management of locally advanced intrahepatic cholangiocarcinoma : Review of literature and pooled analysis

Backgrounds/aims: Approximately 60-80% of patients with intrahepatic cholangiocarcinoma (iCCA) are not suitable for surgical resection due to advanced disease at presentation. This review assesses the role of surgical resection followed by down staging treatment in the management of patients with locally advanced iCCA. Methods: A systematic review and pooled analysis were performed of the relevant published studies published between January 2000-December 2018. The primary outcome measure was overall survival. Secondary outcome measures were rates of clinical benefit, margin-negative (R0) resections, overall and surgery-specific complications, and post-operative mortality. Results: Eighteen cohort studies with 1880 patients were included in the review. The median overall survival in all patients was 14 months (range, 7-18 months). Patients undergoing resection following down staging had significantly longer survival than those who did not (median: 29 vs. 12 months, p<0.001). The Clinical Benefit Rate with this strategy (complete response+partial response+stable disease) was 64% (244/383), ranging from 33-90%. Thirty-eight percent of the patients underwent resections with a 60% R0 resection rate and 6% postoperative mortality. Conclusions: Although the evidence to support the benefits of NAT for iCCA is limited, the review supports the use of down staging treatment and also surgical resection in the cohort with response to NAT in order to improve long-term survival in patients with locally advanced iCCA.