How to manage medullary thyroid carcinoma: current treatment strategies

Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy, representing approximately 2-5% of all thyroid cancers. It develops from the parafollicular C cells of the thyroid gland. Calcitonin, produced by parafollicular C cells, is a highly reliable biomarker for both diagnosis and disease monitoring. MTC commonly spreads to cervical lymph nodes and can also lead to distant metastases. Approximately 25% of MTC cases are hereditary, occurring as part of multiple endocrine neoplasia syndromes. Inherited forms are driven by germline mutations in the RET proto-oncogene. Genetic testing enables identification of RET carriers, whilst the risk associated with specific RET variants helps determine the optimal timing for prophylactic or therapeutic surgery. Surgical management remains the cornerstone treatment for MTC. Nevertheless, recurrent or metastatic disease continues to pose therapeutic challenges, requiring individualized strategies such as locoregional interventions, radiotherapy and systemic therapies. Tyrosine kinase inhibitors, along with selective RET inhibitors, represent the main therapeutic strategies for patients whose tumours show rapid progression. This review summarizes current surgical, locoregional and systemic treatment strategies for sporadic and hereditary MTC, focusing on the role of multi-kinase and selective RET inhibitors.