Treatment for Medullary Thyroid Carcinoma with Lung Metastases
For a patient with medullary thyroid carcinoma (MTC) and lung metastases, cabozantinib or vandetanib should be initiated as first-line systemic therapy if the disease is progressive or symptomatic. 1
First-Line Systemic Therapy Options
Both cabozantinib and vandetanib are approved as first-line treatment for progressive, metastatic MTC with Level I, Grade A evidence. 1 The choice between these agents depends on:
- RET mutation status: If the patient harbors a RET M918T or RAS mutation, cabozantinib offers significant progression-free survival (PFS) and overall survival (OS) advantages over wild-type MTC 1
- Toxicity profile: Both agents have high toxicity rates requiring frequent dose reductions, but vandetanib carries specific cardiac risks including QT prolongation, torsades de pointes, and sudden death 2
- Vandetanib restrictions: Only certified prescribers and pharmacies can prescribe/dispense vandetanib due to its boxed warning for cardiac toxicity 2
When to Initiate Systemic Therapy
Do not start systemic therapy immediately upon detecting metastases. The decision requires assessment of: 1
- Disease progression rate: Calculate calcitonin (CTN) and carcinoembryonic antigen (CEA) doubling times, as these reliably predict disease behavior 1
- Tumor burden: Evaluate total metastatic volume across all sites 3, 4
- Symptom burden: Assess for diarrhea, flushing, or other peptide-related symptoms from hormonal secretion 1
- Performance status: Ensure patient can tolerate multikinase inhibitor toxicities 1
Critical caveat: Systemic therapies for MTC have not been shown to improve overall survival, so evidence-based guidance on exact timing remains limited 1. Some patients exhibit indolent disease with spontaneous regression of certain metastatic sites while others progress 3.
Locoregional Options for Lung Metastases
Before or alongside systemic therapy, consider: 1
- Metastasectomy: May be considered for oligometastatic disease in patients with good performance status, though not standard approach 1
- Radiofrequency ablation (RFA): Option for solitary lung lesions or those causing specific symptoms due to volume/location 1
Second-Line and Beyond
If first-line multikinase inhibitors fail or are not tolerated: 5, 6, 7
- Selective RET inhibitors (selpercatinib or pralsetinib): Approved as second-line options with more favorable side-effect profiles than cabozantinib/vandetanib 5, 7
- Clinical trial enrollment: Should be strongly encouraged for patients with good performance status 1
- Chemotherapy or radionuclide therapy: Little evidence supports their use, but may be considered when multikinase inhibitors are contraindicated 1
Monitoring Requirements
Throughout treatment: 1
- Monitor CTN and CEA levels in early and long-term follow-up 1
- Use multiple imaging modalities to track locoregional and distant metastases 1
- Maintain TSH in normal range (not suppressed, as C cells lack TSH receptors) 1
Common Pitfall
Do not delay systemic therapy in patients with rapidly progressive disease based on calcitonin/CEA doubling times or symptomatic metastases, as the goal shifts from cure to disease control and symptom palliation once distant metastases appear 1, 4. Conversely, avoid premature initiation in truly indolent disease given the lack of OS benefit and significant toxicity burden 1, 3.