Double-Negative α-Fetoprotein and Carbohydrate Antigen 19-9 Predict a Good Prognosis in Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis

Carbohydrate antigen 19-9 (CA19-9) and α-fetoprotein (AFP) are routinely tested in patients with liver malignancies before surgery. However, few reports have explored the relevance of the expression pattern of these 2 tumor markers regarding the prognosis of intrahepatic cholangiocarcinoma (ICC). We herein combined these 2 tumor markers to investigate the influence on ICC malignancy and patient prognosis. METHODS: From March 2009 to December 2019, 519 consecutive patients with newly diagnosed ICC who underwent R0 resection were enrolled and followed. The relationships between clinicopathological parameters and these 2 tumor markers were analyzed. Propensity score matching was used to eliminate the baseline differences. RESULTS: A lower proportion of patients with double-negative AFP and CA19-9 had advanced tumor-node-metastasis stage, larger tumor diameter, multiple tumors, lymph node metastasis, microvascular invasion, and perineural invasion. With propensity score matching, patients were divided into double-negative and non-double-negative groups, with 128 patients in each group, and the 5-year recurrence-free survival and overall survival rates were 33.8 vs 15.2 (P < 0.001) and 45.3 vs 19.0, respectively (P < 0.001). In the multivariate Cox analyses, double negativity for the 2 tumor markers was an independent factor for recurrence-free survival (hazard ratios, 0.578; 95% CI, 0.442–0.755, P < 0.001) and overall survival (hazard ratios, 0.567; 95% CI, 0.434–0.741, P < 0.001). DISCUSSION: Double negativity for CA19-9 and AFP indicated less invasive tumor characteristics in patients with ICC. Patients with double-negative tumor markers achieved better outcomes than those with non-double-negative markers, which is meaningful for prognostic counseling and therapeutic triage.