What is the optimal management plan for a patient with papillary thyroid cancer (PTC) and pulmonary metastases, who has undergone total thyroidectomy and radioactive iodine therapy?

Management of Papillary Thyroid Cancer with Pulmonary Metastases

For patients with papillary thyroid cancer and pulmonary metastases who have undergone total thyroidectomy and initial radioactive iodine therapy, additional high-dose radioactive iodine treatments (100-200 mCi) should be administered for persistent metastatic disease. 1

Current Disease Status Assessment

• The patient has multifocal papillary thyroid cancer (classic type) with a large 6.5 cm focus and lymph node involvement (4/4 nodes positive) 1
• CT chest shows innumerable pulmonary nodules consistent with metastatic disease 1
• Initial RAI therapy with 103 mCi I-131 was administered in February 2022 1
• Thyroglobulin levels have decreased from 1.6 ng/mL to 0.6 ng/mL, indicating partial response to therapy 1

Treatment Recommendations

Additional Radioactive Iodine Therapy

• Patients with distant metastases should receive 100-200 mCi (3.7-7.4 GBq) of I-131 after TSH stimulation 1
• Multiple radioactive iodine treatments are indicated for pulmonary metastases, typically administered every 6-12 months until maximum response is achieved 2
• The pattern of pulmonary metastases (miliary/micronodular vs. macronodular) affects prognosis - micronodular metastases typically respond better to RAI therapy 2

TSH Suppression Therapy

• Aggressive TSH suppression (serum TSH <0.1 μIU/mL) is recommended for patients with persistent structural disease 1
• This requires higher doses of levothyroxine to maintain suppression while monitoring for potential cardiac side effects 1

Surveillance Protocol

• Physical examination, TSH and thyroglobulin measurement with antithyroglobulin antibodies every 6 months initially, then annually if stable 1
• Neck ultrasound should be performed regularly to monitor for locoregional recurrence 1
• Chest imaging (CT scan) should be performed every 6-12 months to assess response of pulmonary metastases 1
• Consider FDG-PET/CT if there is evidence of RAI-refractory disease (rising thyroglobulin with negative RAI scans) 1

Considerations for RAI-Refractory Disease

• Disease should be considered RAI-refractory if lesions lose their ability to concentrate RAI or progress despite RAI avidity 1
• For RAI-refractory disease, systemic therapy with multikinase inhibitors should be considered:
  • Lenvatinib and sorafenib are the standard first-line systemic therapies for RAI-refractory DTC 1
  • Clinical trial enrollment should be encouraged for patients with good performance status 1

Prognosis and Special Considerations

• Pulmonary metastases are more successfully treated if they are RAI-avid, small, and micronodular in pattern 2
• Despite metastatic disease, patients with differentiated thyroid cancer can have prolonged survival with appropriate therapy 1
• The declining thyroglobulin levels suggest some response to initial therapy, which is a positive prognostic indicator 1

Potential Pitfalls and Caveats

• Ensure adequate TSH stimulation before each RAI treatment (either through thyroid hormone withdrawal or recombinant human TSH) 1
• Monitor for potential complications of repeated high-dose RAI therapy, including sialadenitis, bone marrow suppression, and secondary malignancies 2
• Be aware that thyroglobulin levels may not always correlate with disease burden, especially in patients with thyroglobulin antibodies 1
• Consider dosimetry-guided RAI therapy for patients with extensive metastatic disease to maximize therapeutic effect while minimizing toxicity 1