Papillary Thyroid Cancer with Mediastinal Involvement
Papillary thyroid cancer (PTC) involving the mediastinum represents T4b disease (tumor invading mediastinal vessels) and requires total thyroidectomy followed by radioactive iodine (RAI) therapy and external beam radiotherapy (EBRT) when complete surgical excision is not possible or when there is no significant radioiodine uptake. 1
Staging and Classification
Mediastinal involvement in PTC is classified as:
- T4b disease: Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels 1
- This represents locally advanced disease requiring aggressive multimodality treatment 1
Surgical Management
Total thyroidectomy is the mandatory first-line treatment for PTC with mediastinal involvement. 2, 3
Key surgical principles include:
- Complete surgical resection should be attempted when technically feasible, including resection of involved mediastinal structures 1
- The National Comprehensive Cancer Network recommends total thyroidectomy for any PTC with extrathyroidal extension, which includes mediastinal involvement 2
- Therapeutic neck dissection of involved compartments is required for clinically apparent or biopsy-proven lymph node disease 3
- Surgery should only be performed by surgeons experienced in endocrine surgery to minimize complications 2
Preoperative Imaging
Before surgery, obtain:
- CT or MRI with contrast for fixed, bulky, or substernal lesions to map mediastinal extent 3
- Note that iodinated contrast will delay subsequent radioiodine therapy by 4-6 weeks 3
- Vocal cord assessment via ultrasound or laryngoscopy is necessary given the invasive nature 3
Adjuvant Radioactive Iodine Therapy
RAI ablation is indicated after total thyroidectomy for mediastinal involvement. 1, 4, 5
- RAI is most successful when metastases take up radioiodine and are of small size 1
- Initiate levothyroxine immediately post-surgery to maintain TSH suppression (below 0.1 mU/L for high-risk disease like T4b) 2
- Establish baseline thyroglobulin at 6-12 weeks post-thyroidectomy for surveillance 2, 3
External Beam Radiotherapy
EBRT is recommended when complete surgical excision is not possible or when there is no significant radioiodine uptake in the tumor. 1
Specific indications for EBRT in mediastinal PTC:
- Gross residual disease after surgery 6
- Positive surgical margins (R1 or R2 resection) 6
- T4 disease (which includes mediastinal involvement) 6
- Tumors that do not concentrate radioiodine 4, 5
EBRT technique:
- Use 3D conformal radiotherapy or intensity-modulated radiation therapy 1
- Dose: 50-54 Gy for R1 resection, 60 Gy for R2 resection with boost to areas of likely residual disease 1
- Standard fractionation: 1.8-2 Gy daily over 4-6 weeks 1
Systemic Therapy for Refractory Disease
If disease progresses despite surgery, RAI, and EBRT:
Targeted therapy with tyrosine kinase inhibitors is indicated for RAI-refractory progressive disease. 1, 7, 8
- Lenvatinib is FDA-approved for locally recurrent or metastatic, progressive, RAI-refractory differentiated thyroid cancer at 24 mg orally daily 8
- Sorafenib is FDA-approved for the same indication at 400 mg orally twice daily 7
- These agents target RET proto-oncogene and other tyrosine kinase receptors constitutively active in 30-40% of PTC 1
Common Pitfalls to Avoid
- Do not perform lobectomy alone for mediastinal involvement—this is T4b disease requiring total thyroidectomy 2, 3
- Do not delay RAI therapy unnecessarily; if contrast CT is needed, plan timing to minimize delay 3
- Do not omit EBRT when complete resection is not achieved or RAI uptake is poor—this significantly impacts local control 1, 6
- Do not use conventional chemotherapy as first-line systemic therapy; targeted agents (lenvatinib, sorafenib) are superior for RAI-refractory disease 1, 7, 8
Prognosis and Follow-up
- Mediastinal involvement (T4b) carries worse prognosis than localized disease 1
- Bone and brain metastases have the worst prognosis even with aggressive treatment 1
- Lung macro-nodules may benefit from RAI but definitive cure rate is very low 1
- Lifetime follow-up with TSH-stimulated thyroglobulin and neck ultrasound is required 9