Precision management of medullary thyroid carcinoma: a dynamic framework integrating biomarkers, genotyping, and risk stratification

Medullary thyroid carcinoma (MTC) is a heterogeneous neuroendocrine malignancy in which outcomes are shaped by tumor burden, locoregional spread, and molecular context. Precision management therefore requires explicit separation of hereditary MTC driven by germline RET variants from presumed sporadic disease, and a structured integration of serum biomarkers, imaging, pathology, and genotype. This review synthesizes actionable evidence on calcitonin (Ctn) and carcinoembryonic antigen (CEA) baseline values and kinetics, universal germline RET testing, and tumor somatic profiling in advanced or progressive disease, and highlights desmoplastic stromal reaction (DSR) as an underused postoperative risk modifier in sporadic MTC. We propose a clinician-facing three-panel workflow: Panel A standardizes initial evaluation and mandates germline RET testing for all patients; Panel B outlines genotype- and staging-informed surgery and surveillance for hereditary disease, including pediatric carriers; and Panel C provides a staged approach for sporadic MTC in which imaging directs compartment selection and early postoperative DSR and biochemical response tailor surveillance intensity and thresholds for re-staging and re-intervention. By aligning decision nodes with real-world scenarios and using consistent surgical terminology, this framework offers a testable blueprint for precision surgery, surveillance stratification, and genotype-directed systemic therapy.