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

Abstract

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.

Systemic Therapy Is Associated with Improved Oncologic Outcomes in Resectable Stage II/III Intrahepatic Cholangiocarcinoma: An Examination of the National Cancer Database over the Past Decade

“…The total number of patients receiving NAT was very low (6.7%). This is consistent with other published series, including case reports, retrospective analyses, systematic reviews, and meta-analyses, many of which were aimed at downstaging patients who were not initially resectable [ 24 , 36 , 37 ]. Data from our study support the idea that the use of NAT is limited to patients considered to be at high risks of recurrence.…”

“…Available data on the use of NAT for ICC are limited and often extrapolated from studies utilizing NAT to downstage patients for surgical resection. Other data come from case reports, single institution studies, systematic reviews, or meta-analyses on ICC or from studies examining the utilization of NAT for other GI malignancies [ 24 , 36 , 37 ]. In this study, we queried the NCDB to examine the current use and associated outcomes of NAT for the treatment of resectable ICC.…”

Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

“…In a large meta-analysis of 18 studies and 1,880 patients, including eight studies with chemotherapy. Patients who underwent resection following downstaging had significantly longer median survival compared with patients who did not (29 mo vs 12 mo, P < 0.001)[ 49 ]. In another systematic review of 132 patients, 27 patients (20.5%) were downstaged to surgical resection candidates[ 42 ].…”

Surgical Aspects of Intrahepatic Cholangiocarcinoma

“…Regarding neoadjuvant chemotherapy, the evidence is even less persuasive, as there have been no prospective randomized trials assessing the value of neoadjuvant chemotherapy with ICC. A few retrospective studies, consisting of 1880 patients in total, have shown that neoadjuvant chemotherapy can down-stage unresectable ICC, and increase the proportion of patients eligible for surgery (38%, of them 60% R0 resections), in turn improving the outcomes of patients with ICC [ 73 ].…”