Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival

Abstract

Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy.

Patients and methods: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort.

Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34-0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50-0.65 vs. HR 0.63, 95% CI 0.57-0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29-0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46-0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43-0.80; p < 0.001).

Conclusion: In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

Keywords: bile duct cancer; biliary neoplasm; cholangiocarcinoma; hepatic artery pump; locoregional therapy; regional chemotherapy.

FIGURE 1

Intrahepatic cholangiocarcinoma patients (n = 714) by year of diagnosis stratified by (A) clinical presentation (resectable, locally advanced, or metastatic) and (B) treatment (resection, hepatic artery infusion pump [HAIP], or systemic chemotherapy alone [SYS]).

FIGURE 2

Overall survival of resected patients with liver recurrence treated with locoregional therapy versus none. Three patients were lost to follow‐up at the time of recurrence, therefore n = 62. SYS, systemic chemotherapy.

FIGURE 3

Propensity score matched analysis of (A) cumulative incidence of time to liver progression for patients and (B) overall survival of patients receiving hepatic artery infusion pump (HAIP; n = 100) versus systemic chemotherapy alone (SYS; n = 100). Progression is defined as liver progression alone or simultaneous liver and extrahepatic progression.