Thyroid Cancer Treatment Protocols 

Updated: May 18, 2021
  • Author: Eric J Lentsch, MD; Chief Editor: Neetu Radhakrishnan, MD  more...
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Treatment Protocols

Treatment protocols for thyroid cancer are provided below. These include a general treatment approach, [1, 2, 3] as well as treatment recommendations for the three categories of thyroid cancer: differentiated (Hürthle cell, papillary, and follicular), anaplastic (undifferentiated), and medullary thyroid cancer. [1]

General treatment recommendations for thyroid cancer

The treatment of choice for patients diagnosed with thyroid cancer is surgery, when possible. Usually, surgery is followed by treatment with radioiodine and thyroxine therapy. Generally, radiation therapy and chemotherapy do not have a prominent role in the treatment of thyroid cancer.

Radioactive iodine ablation

Postoperative whole-body scintigraphy scan may identify previously unrecognized disease and influence staging. If residual disease is found, adjuvant therapy with radioactive iodine (RAI) may be considered. Ablation of residual normal thyroid tissue facilitates early detection of recurrence based on serum thyroglobulin measurement and/or RAI whole-body scan.

RAI ablation is indicated for patients with any of the following:

  • Large (>4 cm) tumors

  • Known distant metastasis

  • Gross extrathyroid extension

RAI ablation may be considered for tumors with the following characteristics:

  • Moderate-size (1-4 cm) and node positive

  • Grossly multifocal

  • Aggressive, based on histology

  • High risk, based on patient factors (age >45 y, history of head and neck radiation, family history of thyroid cancer)

RAI ablation is not recommended for the following:

  • Small (< 1 cm), solitary tumors

  • Multifocal tumors when all foci are < 1 cm

Early data suggest that RAI is equally effective when used with thyroid hormone withdrawal or with recombinant human thyroid-stimulating hormone (rh-TSH) stimulation. [4]

Thyroid-stimulating hormone (TSH) suppression therapy (levothyroxine)

TSH suppression to < 0.1 mU/L is indicated in intermediate and high-risk disease. TSH maintenance at or slightly below the lower-normal limit (0.3-2 mU/L) may be considered for low-risk disease

Therapy for unresectable gross residual or recurrent disease or metastases

Therapeutic options in patients with unresectable gross residual or recurrent disease or metastases are as follows:

  • Unresectable gross residual/recurrent disease/metastases may be treated with external beam radiation therapy (EBRT)

  • Consider systemic treatment in the context of a clinical trial for persistent metastatic disease despite radioiodine, TSH suppression, and radiotherapy

  • Consider tyrosine kinase inhibitors (TKIs) such as sorafenib 400 mg PO BID [5] or sunitinib 50 mg PO daily for 4wk of a 6-wk cycle [6] for patients who cannot participate in a clinical trial, as well as for those who are not likely to tolerate systemic therapy; since these drugs are usually tumorostatic rather than tumoricidal, they are considered second-line therapy compared with systemic treatments in clinical trials

  • Pazopanib 800 mg PO daily may be considered for progressive or symptomatic metastatic differentiated (Hürthle cell, papillary, and follicular) thyroid carcinoma

  • Randomized phase III clinical trials supporting a TKI benefit in thyroid cancer are currently unavailable; thus, there are no specific regimens

  • Doxorubicin 60 mg/m2 as monotherapy or in combination with cisplatin 40 mg/m2 may be considered for patients who cannot tolerate TKIs or in whom TKIs have failed; however, the efficacy of these, and other cytotoxic drugs, is very limited [7, 8]

  • Selpercatinib 120 mg PO BID (weight < 50 kg) or 160 mg PO BID (weight 50 kg or greater); continue until disease progression or unacceptable toxicity for advanced or metastatic RET fusion–positive thyroid cancer in patients aged 12 years or older who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate) [9]

  • Pralsetinib 400 mg PO qDay on an empty stomach; continue until disease progression or unacceptable toxicity; for advanced or metastatic rearranged during transfection (RET)-mutant MTC in adult and pediatric patients ≥12 years who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). [10]

Treatment recommendations for differentiated thyroid cancer (DTC)

Follicular neoplasm (indeterminate cytology) treatment options are as follows:

  • Consider scintigraphy if not already done, especially in the setting of thyroid-stimulating hormone (TSH) in the low-normal range

  • Hyperfunctioning nodules may be observed; however, if a concordant hyperfunctioning nodule is not identified, lobectomy or total thyroidectomy should be considered

Hürthle cell neoplasm or suspected papillary thyroid cancer (indeterminate cytology) treatment options are as follows:

  • Surgery is ultimately based on patient factors and surgeon expertise (scintigraphy not required)

  • Hemithyroidectomy may be considered for patients with an isolated, indeterminate, solitary nodule

  • If papillary thyroid cancer (PTC) diagnosis is made following hemithyroidectomy, completion thyroidectomy is recommended

  • The surgical risks of two-stage thyroidectomy and total or near-total thyroidectomy are similar

Papillary and follicular thyroid cancer stages I-IV (confirmed by cytology) treatment options are as follows [1, 11, 12, 13] :

  • Surgery is ultimately based on patient factors and surgeon expertise

  • Thyroid lobectomy alone is sufficient for small (< 1 cm), unifocal, intrathyroidal carcinomas in the absence of prior head and neck radiation, familial thyroid carcinoma, or clinically detectable cervical nodal metastases. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)—formerlyclassified as encapsulated follicular variant of PTC—requires only lobectomy.

  • Lobectomy may be considered for 1-4 cm, low risk, unifocal, intrathyroid tumors in the absence of prior head and neck radiation, cervical or distant nodal metastasis, and extrathyroidal extension; however, total thyroidectomy may be chosen to enable RAI therapy or to enhance follow-up, based upon disease features and/or patient preference.

  • Total thyroidectomy is recommended for tumors >4 cm in diameter

  • Therapeutic central neck dissection when cervical lymph nodes are involved

  • When lateral cervical lymph nodes have biopsy-proven disease, therapeutic central and lateral compartment neck dissection should be performed.

  • Prophylactic unilateral or bilateral central neck dissection may be considered in clinically N0 disease, especially for advanced primary tumors (T3 or T4)

Locally recurrent or metastatic, progressive DTC treatment options are as follows:

  • Sorafenib and lenvatinib are VEGF inhibitors approved for DTC refractory to RAI treatment [14, 15]

  • Sorafenib: 400 mg PO q12h at least 1 h ac or 2 h pc

  • Lenvatinib: 24 mg PO once daily with or without food

  • Continue treatment until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs

Treatment recommendations for anaplastic (undifferentiated) thyroid cancer

Therapeutic options in anaplastic thyroid cancer (ATC) are as follows:


Because most patients with ATC have advanced disease at the time of diagnosis, surgery is often not indicated; however, if the tumor appears to be localized to the thyroid, lobectomy with wide margins of ipsilateral soft tissues is recommended, often in conjunction with postoperative adjuvant radiotherapy or combined-modality therapy

As long as the tumor is small and entirely confined to the thyroid, total thyroidectomy does not appear to improve survival, as compared with lobectomy, and is associated with a higher risk for complications

Surgical debulking may provide symptomatic relief for patients with very large tumors and significant airway compression

Combined-modality therapy

Combined-modality options are as follows:

  • Consider primary combined radiotherapy and chemotherapy for locally advanced, unresectable disease.

  • Since there are no randomized, controlled trials available to definitively prove the therapeutic efficacy of combined-modality therapy, most management strategies are based on single-institution phase II trials and retrospective reviews; thus, there are no standard regimens.

  • Doxorubicin is the only cytotoxic chemotherapy specifically approved by the US Food and Drug Administration for use in ATC [16] ; a typical doxorubicin-based regimen includes doxorubicin 20 mg once weekly given prior to the first radiotherapy session [8]  Other agents with the greatest established clinical activity in metastatic ATC are the taxanes paclitaxel or docetaxel and perhaps also platins. [16]

  • Chemotherapy is followed by hyperfractionated radiation and often by an additional round of chemotherapy after radiotherapy completion

  • Doxorubicin has also been given concurrently with radiation therapy as a radiosensitizer

  • Consider surgical resection for patients who have a good response to treatment

Palliative care

Even with aggressive treatment, anaplastic thyroid cancer is almost always fatal, and there is no effective therapy for metastatic disease. End-of-life issues, comfort, and care options are essential considerations during initial treatment planning.

Treatment recommendations for medullary thyroid cancer

Surgical options in medullary thyroid cancer are as follows [20] :

  • Total thyroidectomy with prophylactic or therapeutic central neck dissection (level VI) is considered the standard of care for all patients with medullary thyroid cancer

  • Assessment for metastatic disease by preoperative imaging of the neck, chest, and liver is recommended for patients with nodal metastasis and for those with serum calcitonin >400 pg/mL

  • Therapeutic compartmental lateral neck dissection should be attempted for patients with minimal or no distant metastasis

  • In patients with distant metastasis or advanced local disease, less aggressive neck surgery that preserves speech and swallowing function may be appropriate

  • Palliative debulking surgery may be considered to relieve tracheal compression and local pain

  • Preoperative exclusion or treatment of a concomitant pheochromocytoma is critical, given its high risk of surgery and anesthesia complications

  • A second surgery, possibly with remedial central neck dissection, may be considered for patients with evidence of recurrent or persistent disease, rising serum calcitonin levels in the setting of an inadequate initial operation, or threatening tracheal invasion or compression; however, reoperation carries a higher risk of complications, including thoracic duct leak, recurrent laryngeal nerve injury, and hypoparathyroidism

Thyroxine replacement therapy [20] (standard dosing with thyroxine replacement) should be initiated postoperatively with the goal of maintaining euthyroidism. In contrast to epithelial cell–derived thyroid cancers, TSH suppression to lower-than-normal levels is not indicated, since C-cells are not TSH responsive. Similarly, radioactive iodine [RAI] is not indicated in medullary thyroid cancer, because C-cells do not concentrate iodine.

Therapy for unresectable or recurrent disease or for metastases is as follows [20] :

  • Radiotherapy may be considered for patients with gross residual disease after surgery and for those with distant metastasis

  • The role of external beam radiation therapy (EBRT) in M0 or minimal M1 disease is controversial

  • Consider systemic therapy in the context of a clinical trial for patients with progressive metastatic disease who cannot be treated with surgery or radiotherapy

  • The low incidence of medullary thyroid cancer has limited widespread clinical consensus, as well as the ability to conduct large, definitive, randomized, controlled trials; thus, there are no standard regimens

  • The TKIs vandetanib and cabozantinib have been approved by the FDA for progressive, metastatic medullary thyroid cancer

  • Selpercatinib is approved for advanced or metastatic RET-mutated MTC in patients aged 12 years or older who require systemic therapy [9]

Dosages of TKIs for metastatic medullary thyroid cancer are as follows:

  • Vandetanib: 300 mg PO daily

  • Cabozantinib: 140 mg PO daily

  • Selpercatinib: 120 mg PO BID (weight < 50 kg) or 160 mg PO BID (weight 50 kg or greater)

  • Pralsetinib: 400 mg PO qDay on an empty stomach

  • Dosage adjustment for these TKIs may be required depending on toxicity and coadministered drugs

Special diagnostic considerations

Nondiagnostic fine-needle aspiration (FNA) can be managed as follows [21] :

  • Repeat ultrasonographically guided FNA; if repeat FNA is nondiagnostic, may consider close follow-up or surgery

  • Surgery should be more strongly considered if the nodule is solid

Nodules < 1 cm can be managed as follows [21] :

  • Routine FNA is not recommended unless there are abnormal lymph nodes, suspicious ultrasonographic findings (solid hyperechoic with microcalcifications), or a high-risk history (radiation exposure, personal or family history of thyroid cancer, incidental 18-F-fluorodeoxyglucose [18FDG]–positron emission tomography [PET]–positive nodules)

  • Abnormal lymph nodes should be aspirated under ultrasonographic guidance

Multiple nodules >1 cm can be managed as follows [21] :

  • Aspirate any that are suspicious on ultrasonography

  • If spongiform in appearance (multiple ultrasonographically similar nodules with no intervening normal parenchyma), aspirate the largest nodules and observe the others with serial ultrasonographic exams

  • In the presence of low or low-normal TSH, scintigraphy should be compared to ultrasonographic images

  • Isofunctioning or hypofunctioning nodules >1-1.5 cm should be aspirated