Dynamic risk stratification-guided management of medullary thyroid carcinoma: integrating surgical precision with RET-targeted therapies and molecular surveillance

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine neoplasm derived from parafollicular C cells of the thyroid gland, primarily driven by alterations in the RET oncogene. This review focuses on the current advances in treatment modalities for MTCs, encompassing surgical interventions, targeted therapy, postoperative surveillance, and future challenges. Total thyroidectomy is the primary curative approach for MTCs. However, the extent of lymph node dissection, particularly lateral neck dissection, remains controversial. Postoperative surveillance involves monitoring serum calcitonin and carcinoembryonic antigen levels, imaging assessments, and dynamic risk stratification to detect recurrence. Drug therapy offers an alternative approach in cases of challenging surgical scenarios or advanced MTCs. Multi-kinase inhibitors (e.g. vandetanib and cabozantinib) have shown increased survival outcomes for metastatic MTCs and are approved as effective treatment options. More recently, selective RET inhibitors like selpercatinib and pralsetinib have demonstrated higher efficacy and better tolerability. Despite these advances, challenges persist in managing MTCs, including addressing biochemical recurrence, determining surgical scope, considering immunotherapy, and treating advanced cases. Personalized medicine approaches, incorporating genetic screening, and innovative therapies, are essential for improving survival and quality of life in MTC patients.