Double negativity for carbohydrate antigen 19-9 (CA19-9) and α-fetoprotein (AFP) was found to be an independent factor for recurrence-free survival and overall survival in intrahepatic cholangiocarcinoma, as published in the journal Clinical and Translational Gastroenterology.

This finding is meaningful for the prognostic counseling and therapeutic triage of patients, Zhang Xiaoyun, MD, and the coauthors of the study said.

CA19-9 is a tetrasaccharide attached to O-glycans on the cell surface that plays a vital role in cell-to-cell recognition and is used as a tumor marker. AFP is a protein expressed in the liver during fetal development, and is also a tumor marker in hepatic malignancies.

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Both CA19-9 and AFP are routinely tested before surgery in cancers of the liver, but their relevance for the prognosis of intrahepatic cholangiocarcinoma has not been extensively explored. 

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To investigate the potential role of these 2 markers in the malignancy and prognosis of intrahepatic cholangiocarcinoma, a team of researchers from China followed 519 patients diagnosed between March 2009 and December 2019 who underwent R0 resection.

They found that a smaller number of patients with double-negative CA19-9 and AFP had advanced tumor-node-metastasis stage, lymph node metastasis, microvascular invasion, larger tumor diameter, multiple tumors, and perineural invasion than those who were nondouble-negative. 

The 5-year recurrence-free survival rate was 33.8 in double-negative patients compared to 15.2 in nondouble-negative patients. Similarly, the overall survival rate was much higher in double-negative patients, at 45.3 compared to 19 in nondouble-negative patients. 

“Double negativity for CA19-9 and AFP indicated less invasive tumor characteristics in patients with ICC,” the researchers wrote, concluding that it led to better outcomes.


Zhang X, Zhou Y, Wu Z, et al. Double-negative α-fetoprotein and carbohydrate antigen 19-9 predict a good prognosis in intrahepatic cholangiocarcinoma: a propensity score matching analysis. Clin Transl Gastroenterol. 2021;12(11):e00425. doi:10.14309/ctg.0000000000000425