What is the treatment approach for medullary thyroid carcinoma (MTC)?

Treatment Approach for Medullary Thyroid Carcinoma (MTC)

Surgery is the main treatment for medullary thyroid carcinoma, as no known curative systemic therapy exists. 1 The approach varies based on disease stage, tumor characteristics, and whether the disease is sporadic or hereditary.

Initial Surgical Management

For patients with MTC, the surgical approach depends on tumor size and extent:

• For tumors ≥1 cm or bilateral disease: Total thyroidectomy and bilateral central neck dissection (level VI) 1
• For tumors <1 cm with unilateral disease: Total thyroidectomy (neck dissection can be considered) 1
• For hereditary MTC: Prophylactic total thyroidectomy based on RET mutation risk level:
  • Highest Risk (Level D mutations - codons 883,918, compound heterozygous): Surgery in first year of life 2
  • High Risk (Level B mutations - codons 609,611,618,620,630,634): Surgery by age 5 years 2
  • Moderate Risk (Level A mutations - codons 768,790,791,804,891): Annual monitoring with surgery if abnormalities develop 2

Preoperative Evaluation

• Serum calcitonin and CEA measurements 1
• Neck ultrasound 1
• RET proto-oncogene mutation testing (for all patients with MTC) 1
• Screening for pheochromocytoma (MEN 2A and 2B) and hyperparathyroidism (MEN 2A) 1
  • Critical safety point: Pheochromocytomas must be treated before thyroid surgery to avoid hypertensive crisis 1, 2

Postoperative Management

• Levothyroxine therapy (maintain TSH in normal range, not suppressed) 1
• Monitor serum calcitonin and CEA levels 2-3 months after surgery 2
• Additional imaging if calcitonin >150 pg/mL or elevated CEA 2

Management of Advanced/Metastatic Disease

For patients with unresectable locally advanced or metastatic MTC:

1. Molecular testing: RET mutation testing to guide therapy 1

2. Systemic therapy options:

   • For RET-mutant MTC:
     • Selective RET inhibitors (selpercatinib, pralsetinib) - FDA approved for advanced/metastatic RET-mutant MTC 1
   • For symptomatic or progressive disease:
     • Vandetanib - FDA approved for symptomatic or progressive unresectable locally advanced or metastatic MTC 3
     • Important safety warning: Vandetanib can cause QT prolongation, Torsades de pointes, and sudden death 3

3. Locoregional therapies for isolated metastases when feasible 2

Special Considerations

• Hereditary MTC: Genetic counseling and screening of family members for RET mutations 1
• MEN 2 syndromes: Annual screening for pheochromocytoma and hyperparathyroidism 2
• Surgical expertise: Referral to surgeons experienced in thyroid surgery, especially for pediatric patients 2

Prognostic Factors

• Age at diagnosis (<40 years has better prognosis) 1
• Tumor stage (AJCC staging) 1
• RET mutation status (exon 16 mutations associated with more aggressive disease) 1
• Postoperative calcitonin levels (persistent elevation indicates residual disease) 1

The treatment of MTC requires a multidisciplinary approach, with surgery as the cornerstone of management and targeted therapies for advanced disease. Early identification of hereditary forms and appropriate timing of prophylactic surgery in mutation carriers are crucial for improving outcomes.