Combined Detection of Preoperative Serum Calcitonin and Carcinoembryonic Antigen in Medullary Thyroid Carcinoma: A Retrospective Multicenter Cohort Study

The aim of this study was to investigate the clinical value of combined detection of preoperative serum calcitonin (Ctn) and carcinoembryonic antigen (CEA) for diagnosing medullary thyroid carcinoma (MTC), as well as predicting lymph node metastases and prognosis, compared with the value of detection of either marker alone.

This retrospective multicenter cohort study included patients with thyroid nodules who underwent preoperative measurements of serum Ctn and CEA at six medical centers between 2012 and 2024. Receiver operating characteristic (ROC) curves were analyzed to compare the diagnostic performances of Ctn, CEA, and their combination.

A total of 13,272 patients were included in the study, comprising 115 with MTC, 10,845 with papillary thyroid carcinoma, and 2312 with benign nodules. For diagnosing MTC, the area under the ROC curve (AUC) values for Ctn and CEA alone were 0.992 and 0.983, respectively, while the combination of the two markers achieved the highest AUC of 0.999. Ctn had a higher positive predictive value (PPV) for MTC diagnosis than CEA (51% vs. 31%), and the combination did not improve the PPV (46%) compared with Ctn alone. For predicting cervical and lateral neck lymph node metastases in MTC, the combination had a higher AUC than Ctn or CEA alone (0.735 vs. 0.708 vs. 0.655 and 0.769 vs. 0.707 vs. 0.675). The combination also had a higher AUC for predicting recurrence than Ctn or CEA alone (0.734 vs. 0.642 vs. 0.611).

Compared with the detection of either marker alone, the combined detection of Ctn and CEA improved the diagnostic accuracy for MTC but did not enhance the PPV. The combined detection also improved the predictive accuracy for cervical and lateral lymph node metastases and disease recurrence.