Neoadjuvant Chemotherapy for High-risk Intrahepatic Cholangiocarcinoma – Does Pathologic Response Mean Better Outcomes?

Abstract

Introduction: We analyzed our experience with neoadjuvant chemotherapy (NAC) for patients with high-risk intrahepatic cholangiocarcinoma (IHC) focusing on the significance of pathologic response as a predictor of survival. Methods: A single-institution, prospectively maintained database was analyzed for patients with IHC who were treated with chemotherapy prior to definitive resection from 2006-2019. The tumor specimens were assessed for treatment response and survival outcomes were analyzed. Major pathologic response was defined as < 50% viable tumor cells. Results: Our study includes 45 patients who received NAC followed by hepatectomy for IHC, 40 of which (89%) were considered stage III at time of diagnosis. Indications for NAC consisted of nodal involvement or poor performance status in 38 patients (84%) and initially unresectable disease in 7 patients (16%). NAC regimens included: gemcitabine and cisplatin (64%); gemcitabine, cisplatin and nab-paclitaxel (27%); gemcitabine and carboplatin (4%); and FOLFOX (4%). For the entire study cohort, median overall survival (OS) was 45 months and recurrence free survival (RFS) was 9.7 months. 39% of patients had major response, including 2 with complete response, and 61% had minor response. Pathologic response was not associated with median RFS (11 months major response vs. 14 months minor response, p=0.7) or OS (44 months major response vs. 75 months minor response, p=0.9) (Figure 1). Conclusions: Pathologic response to NAC is not associated with improved survival. Still, OS following NAC for these high-risk patients with IHC is encouraging. Future studies should focus on objective biomarkers of response that may better prognosticate survival.