Patients with medullary thyroid cancer (MTC) who are treated with selpercatinib and have an objective tumor response can have a lasting increase in serum carcinoembryonic antigen (CEA) levels, according to a new case study published in European Thyroid Journal.

“The mechanism behind this unexpected rise in CEA level remains unknown,” the researchers wrote. Normally, levels of CEA and calcitonin (CT) in the serum frequently decrease in parallel after an efficient treatment has been started.

In the present study, a team of researchers led by Sophie Leboulleux, MD, from Gustave Roussy in Villejuif, France reported the case of 2 patients with RET-mutant progressive metastatic MTC who were both treated with selpercatinib. 

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Both patients had an objective tumor response with rapid clinical improvement and rapid and dramatic decreases in CT levels. However, their CEA levels gradually increased following the start of the treatment.

“In conclusion, clinicians should be aware that CEA levels can increase in some patients after successful treatment of RET-mutant MTC patients with selpercatinib,” the researchers wrote.

They said that they will conduct further studies to determine the frequency of this phenomenon, and added that in the future, only levels of CT might be measured when following up patients treated with selpercatinib.

Selpercatinib is a selective receptor tyrosine kinase RET inhibitor that is approved by the US Food and Drug Administration to treat patients with advanced or metastatic MTC.

CT and CEA produced by neoplastic C-cells are both valuable tumor markers in patients with MTC. CT is specific to MTC but CEA is not, and its serum concentration can also increase in case of other malignant tumors and other benign conditions such as infections, inflammatory bowel disease, pancreatitis, and cirrhosis of the liver.


Bardet S, Ciappuccini R, Lamartina L, Leboulleux S. Unusual increase in carcinoembryonic antigen despite response to selpercatinib in two patients with medullary thyroid cancer. Eur Thyroid J. Published online January 1, 2022. doi:10.1530/ETJ-21-0104