Abstract:Background and Aims Medullary thyroid carcinoma (MTC) is an aggressive malignancy that is frequently associated with cervical lymph node metastasis, significantly affecting patient prognosis. However, the risk factors for lateral cervical lymph node metastasis (LLNM) in MTC remain inconclusive. This study aims to identify the risk factors associated with LLNM in MTC patients, in order to inform individualized surgical decision-making.Methods The clinicopathologic data of 242 patients with MTC who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from 2011 to 2019 were retrospectively collected. The relationships between preoperative tumor markers, including calcitonin and carcinoembryonic antigen (CEA), and LLNM were evaluated. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for LLNM.Results Preoperative calcitonin level was significantly associated with tumor diameter, the number of lymph node metastases, and the extent of lymph node involvement, while preoperative CEA level was significantly associated with tumor diameter (all P<0.05). The area under the ROC curve for preoperative calcitonin in diagnosing LLNM was 0.750 (P=0.000), with an optimal cutoff value of 266.00 ng/L (sensitivity 0.854, specificity 0.577). The diagnostic value of preoperative CEA for LLNM was limited. Univariate analysis showed that sex, extracapsular extension, T stage, central lymph node metastasis (CLNM), bilateral lesions, preoperative calcitonin, tumor diameter, and multifocality were significantly associated with LLNM in MTC patients (all P<0.05). Multivariate analysis revealed that CLNM (OR=17.645, 95% CI=7.728-40.290) and preoperative calcitonin ≥266.00 ng/L (OR=7.832, 95% CI=3.132-19.582) were independent risk factors for LLNM.Conclusion CLNM and elevated preoperative calcitonin level are closely associated with LLNM in patients with MTC. The combination of these two indicators may help identify high-risk patients for LLNM, thereby and promoting individualized and precise treatment strategies for MTC.