Postoperative Treatment of Thyroid Cancer
Risk-Stratified Approach to Differentiated Thyroid Cancer (DTC)
Postoperative treatment of differentiated thyroid cancer centers on three pillars: radioactive iodine (RAI) ablation based on risk stratification, TSH suppression therapy tailored to recurrence risk, and structured surveillance with thyroglobulin monitoring and neck ultrasound. 1
Radioactive Iodine (RAI) Ablation
The decision to administer RAI depends critically on risk stratification performed immediately after surgery:
High-risk patients (T3-T4 tumors, extrathyroidal extension, lymph node metastases, incomplete resection, or distant metastases) should receive RAI ablation at doses of 100-200 mCi (3.7-7.4 GBq) 1
Intermediate-risk patients (T1 >1 cm or T2 tumors, aggressive histology, or multifocal disease) require individualized decisions, though RAI is generally recommended 1
Very low-risk patients (unifocal T1 ≤1 cm, intrathyroidal, favorable histology, no metastases) should NOT receive RAI ablation 1
Preparation for RAI can be accomplished with recombinant human TSH (rhTSH) while continuing levothyroxine, which is equally effective as thyroid hormone withdrawal and avoids hypothyroid symptoms. 1 Lower doses of 50 mCi may be equally effective as 100 mCi when using rhTSH preparation, even with lymph node metastases. 1
TSH Suppression Therapy with Levothyroxine
Levothyroxine serves dual purposes: hormone replacement and TSH suppression to reduce tumor growth stimulus. The degree of suppression must be risk-stratified:
High-risk patients with persistent structural disease: TSH <0.1 mIU/L 1, 2, 3
Intermediate-risk patients with biochemical incomplete or indeterminate response: TSH 0.1-0.5 mIU/L 1, 2
Low-risk patients with excellent response to therapy: TSH 0.5-2.0 mIU/L (normal range) 1, 2
Initiate levothyroxine immediately after surgery, with first TSH measurement at 6 weeks postoperatively, then every 6 weeks after dose adjustments until target achieved. 2 Over-suppression increases risks of atrial fibrillation (especially in elderly), decreased bone mineral density, and other thyrotoxicosis complications. 3
Surveillance Protocol
At 2-3 months post-treatment, assess adequacy of TSH suppression with thyroid function tests (FT3, FT4, TSH). 1
At 6-12 months, perform comprehensive evaluation including:
- Physical examination
- Neck ultrasound
- Basal and rhTSH-stimulated serum thyroglobulin (Tg) measurement
- Consider diagnostic whole body scan 1
For patients with excellent response (undetectable basal and stimulated Tg <0.2 ng/mL, negative anti-Tg antibodies, negative neck ultrasound), annual follow-up consists of:
- Physical examination
- Basal serum Tg on levothyroxine therapy
- Neck ultrasound 1
High-sensitivity Tg assays (<0.2 ng/mL) can replace TSH-stimulated testing to verify absence of disease. 1
Medullary Thyroid Cancer (MTC)
After total thyroidectomy for MTC, levothyroxine should maintain TSH in the normal range (0.5-2.0 mIU/L), NOT suppressed, because C cells lack TSH receptors. 1, 2
Postoperative surveillance relies on calcitonin (CT) and CEA monitoring:
- If post-surgery CT is undetectable after provocative testing (pentagastrin or calcium), repeat CT every 6 months for 2-3 years, then annually 1
- CT <150 pg/mL: limit evaluation to careful neck ultrasound 1
- CT >150 pg/mL: screen for distant metastases with cross-sectional imaging 1
For advanced/metastatic MTC, vandetanib is FDA-approved and should be considered for patients with incurable disease. 1
Poorly Differentiated Thyroid Cancer (PDTC)
PDTC requires aggressive postoperative management given its intermediate prognosis between DTC and anaplastic cancer:
- Initiate TSH suppressive therapy with levothyroxine immediately after surgery 1
- Most PDTCs respond poorly to RAI and are FDG-PET positive 1
- Consider external beam radiotherapy (EBRT) for unresectable or persistent locoregional disease after surgery 1
- Chemotherapy (cisplatin, doxorubicin) achieves only transient, incomplete responses 1
- Strongly encourage enrollment in clinical trials of novel therapies 1
Anaplastic Thyroid Cancer (ATC)
For the rare patient with resectable ATC, postoperative treatment consists of high-dose EBRT with or without concurrent chemotherapy, delivered as soon as possible after surgery. 1 Intensity-modulated radiation therapy (IMRT) is the recommended approach. 1 Timely multidisciplinary team discussion is essential given the aggressive nature and poor prognosis. 1
Advanced/Metastatic Disease Management
RAI-Refractory DTC
Lenvatinib and sorafenib are standard first-line systemic therapies for RAI-refractory DTC with progressive disease. 1, 4 Lenvatinib is indicated for locally recurrent or metastatic, progressive, RAI-refractory DTC. 4
Criteria for RAI-refractory disease include:
- Non-RAI-avid lesions on diagnostic imaging
- Loss of ability to concentrate RAI
- Progression despite RAI avidity 1
Before initiating multikinase inhibitors, ensure:
- TSH suppression (<0.1 mIU/L) is maintained for all patients with persistent structural disease 1
- Careful discussion with patient regarding expected benefits versus risks (hypertension, proteinuria, diarrhea, hand-foot syndrome, hypothyroidism) 4
- Monitoring for serious adverse effects including hemorrhage, cardiac dysfunction, hepatotoxicity, and reversible posterior leukoencephalopathy syndrome 4
Locoregional Recurrence
Surgery combined with RAI therapy is the primary treatment for recurrent locoregional disease. 1 Supplement with EBRT if surgery is incomplete or RAI uptake is absent. 1
Distant Metastases
RAI-avid, small lung metastases have the best prognosis and may be cured with RAI therapy. 1 For non-RAI-avid or progressive metastases, consider locoregional therapies (surgery, EBRT, radiofrequency ablation) for oligometastatic disease or symptomatic lesions. 1 Bone metastases may benefit from bisphosphonates or denosumab combined with locoregional treatments. 1
Critical Pitfalls to Avoid
- Do not over-suppress TSH in low-risk patients with excellent response—this increases cardiovascular and bone complications without oncologic benefit 1, 2, 3
- Do not suppress TSH in medullary thyroid cancer—C cells lack TSH receptors, making suppression futile and harmful 1, 2
- Do not administer RAI to very low-risk DTC patients—this provides no benefit and exposes patients to unnecessary radiation 1
- Do not delay EBRT after surgery in anaplastic thyroid cancer—early radiation is critical for any chance of locoregional control 1
- Monitor thyroid function regularly in patients on lenvatinib or sorafenib—these drugs commonly cause hypothyroidism requiring levothyroxine dose adjustment 4