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Thyroid cancer includes the following four main types:
For clinical management of the patient, thyroid cancer is generally divided into the following two categories:
Well-differentiated tumors (papillary and follicular thyroid cancer) are highly treatable and usually curable. Poorly differentiated and undifferentiated thyroid tumors (anaplastic thyroid cancer) are less common, aggressive, metastasize early, and have a poorer prognosis. Medullary thyroid cancer is a neuroendocrine cancer that has an intermediate prognosis.
The thyroid gland may occasionally be the site of other primary tumors, including sarcomas, lymphomas, epidermoid carcinomas, and teratomas. The thyroid may also be the site of metastasis from other cancers, particularly of the lung, breast, and kidney.
Incidence and Mortality
Estimated new cases and deaths from thyroid cancer in the United States in 2018:
Thyroid cancer affects women more often than men and usually occurs in people aged 25 to 65 years. The incidence of this malignancy has been increasing over the last decade. Thyroid cancer commonly presents as a so-called cold nodule. It is detected as a palpable thyroid gland during a physical exam and evaluated with iodine I 131 scans; scintigraphy shows that the isotope is not taken up in an area of the gland. The overall incidence of cancer in a cold nodule is 12% to 15%, but it is higher in people younger than 40 years and in people with calcifications present on preoperative ultrasonography.[3,4]
Thyroid gland tissue envelops the upper trachea just below the thyroid and cricoid cartilages that make up the larynx. The gland has an isthmus and often asymmetric right and left lobes; usually four parathyroid glands lie posteriorly. When swallowing, the thyroid may be felt to rise with the larynx—most commonly in the presence of a disease process.
Anatomy of the thyroid and parathyroid glands.
Patients with a history of radiation therapy administered in infancy or childhood for benign conditions of the head and neck (such as enlarged thymus, tonsils, or adenoids; or acne) have an increased risk of cancer and other abnormalities of the thyroid gland. In this group of patients, malignancies of the thyroid gland appear as early as 5 years after radiation therapy and may appear 20 or more years later. Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[6,7,8]
Other risk factors for thyroid cancer include the following:
Diagnostic and Staging Evaluation
The following tests and procedures may be used in the diagnosis and staging of thyroid cancer:
Prognostic Factors for Well-differentiated Thyroid Cancer
Age appears to be the single most important prognostic factor. The prognosis for differentiated carcinoma (papillary or follicular) without extracapsular extension or vascular invasion is better for patients younger than 40 years.[12,13,14,15,16]
Patients considered at low risk according to age, metastases, extent, and size risk criteria include women younger than 50 years and men younger than 40 years without evidence of distant metastases. The low-risk group also includes older patients with primary papillary tumors smaller than 5 cm without evidence of gross extrathyroid invasion, and older patients with follicular cancer without major capsular invasion or blood vessel invasion. Using these criteria, a retrospective study of 1,019 patients showed that the 20-year survival rate was 98% for low-risk patients and 50% for high-risk patients.
A retrospective surgical series of 931 previously untreated patients with differentiated thyroid cancer found that age older than 45 years, follicular histology, primary tumor larger than 4 cm (T2–T3), extrathyroid extension (T4), and distant metastases were adverse prognostic factors.[17,18] Favorable prognostic factors included female gender, multifocality, and regional lymph node involvement. Other studies, however, have shown that regional lymph node involvement had no effect [19,20] or had an adverse effect on survival.[15,16,21]
Another retrospective series of 1,807 patients found that the presence of distant metastases was most predictive of survival, followed by age. An age cutoff of 55 years was identified as most predictive of survival. This led to an international multi-institutional validation of age 55 years as a cutoff for risk stratification in the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system for well-differentiated thyroid cancer. This analysis of 9,484 patients was responsible for the change in age cutoff from 45 years to 55 years in the AJCC Cancer Staging Manual, 8th edition, using AJCC/UICC staging for well-differentiated thyroid cancer.
The prognostic significance of lymph node status is controversial. Use of sentinel lymph node biopsy may aid in identifying patients with occult metastases who might benefit from central neck dissection.
Diffuse, intense immunostaining for vascular endothelial growth factor in patients with papillary cancer has been associated with a high rate of local recurrence and distant metastases. An elevated serum thyroglobulin level correlates strongly with recurrent tumor when found in patients with differentiated thyroid cancer during postoperative evaluations.[26,27] Serum thyroglobulin levels are most sensitive when patients are hypothyroid and have elevated serum thyroid-stimulating hormone levels. Expression of the tumor suppressor gene p53 has also been associated with an adverse prognosis for patients with thyroid cancer.
(Refer to the Clinical Features and Prognosis section of the Medullary Thyroid Cancer section and the Clinical Features and Prognosis section of the Anaplastic Thyroid Cancer section of this summary for more information about prognosis.)
Other PDQ summaries containing information related to thyroid cancer include the following:
In thyroid cancer, cell type is an important determinant of prognosis and treatment. The thyroid has two cell types: follicular cells and parafollicular C cells. The management of thyroid cancer depends on the cell of origin and how well the integrity of the cell type is maintained. The four main types of thyroid cancer are divided into the following two categories for clinical management:
Differentiated (follicular cell) thyroid cancers.
Parafollicular C cell thyroid cancers.
Other types (not derived from thyroid cells).
Definitions of TNM
The American Joint Committee on Cancer has designated staging by the TNM (tumor, node, metastasis) classification to define thyroid cancer.[1,2] Definitions of TNM stages for each type of thyroid cancer are described in the following sections of this summary:
Standard treatment options for thyroid cancer are described in Table 1.
Clinical Features and Prognosis
The clinical features and prognosis of well-differentiated thyroid tumors vary by stage.
Most papillary cancers have some follicular elements. These follicular elements may outnumber the papillary formations, but they do not change the prognosis.
Follicular adenomas, which are characterized by their lack of invasion through the capsule into the surrounding thyroid tissue, must be distinguished from follicular thyroid carcinoma. While follicular cancer has a good prognosis, it is less favorable than that of papillary carcinoma. The 10-year survival is better for patients with follicular carcinoma without vascular invasion than it is for patients with vascular invasion.
Papillary carcinomas metastasize more frequently to regional lymph nodes than to distant sites. Follicular carcinomas more commonly invade blood vessels and metastasize hematogenously to the lungs and to the bone rather than through the lymphatic system. When metastases occur, treatment with radioiodine is initially effective, but prognosis worsens as resistance to radioiodine ensues.
Staging and prognosis of papillary and follicular thyroid cancer are determined by the age and site of the disease. The clinical features and prognoses for papillary thyroid cancer include the following:
Hürthle cell carcinoma is a variant of follicular carcinoma with a similar prognosis and is treated in the same way as equivalent stage non-Hürthle cell follicular carcinoma.
Stage Information for Papillary and Follicular Thyroid Cancer
Standard Treatment Options for Papillary and Follicular Thyroid Cancer
Localized/regional papillary and follicular thyroid cancer
Surgery is the therapy of choice for all primary lesions. Surgical options include total thyroidectomy or lobectomy. The choice of procedure is influenced mainly by the age of the patient and the size of the nodule. Survival results with the two procedures are similar for early-stage disease, with differences in the rates of surgical complications and local recurrences.[2,3,4,5,6,7,8]
Standard treatment options for localized/regional papillary and follicular thyroid cancer
Standard treatment options for localized/regional papillary and follicular thyroid cancer include the following:
The objective of surgery is to completely remove the primary tumor, while minimizing treatment-related morbidity, and to guide postoperative treatment with RAI. The goal of RAI is to ablate the remnant thyroid tissue to improve the specificity of thyroglobulin assays, which allows the detection of persistent disease by follow-up whole-body scanning. For patients undergoing RAI, removal of all normal thyroid tissue is an important surgical objective. Additionally, for accurate long-term surveillance, RAI whole-body scanning and measurement of serum thyroglobulin are affected by residual, normal thyroid tissue, and in these situations, near total or total thyroidectomy is required. This approach facilitates follow-up thyroid scanning.
Total thyroidectomy is often used because of the high incidence of multicentric involvement of both lobes of the gland and the possibility of dedifferentiation of any residual tumor to the anaplastic cell type.
Evidence (total thyroidectomy):
Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of previous head and neck irradiation or radiologically or clinically involved cervical nodal metastases. This procedure is associated with a lower incidence of complications, but approximately 5% to 10% of patients will have a recurrence in the thyroid after a lobectomy.
Abnormal regional lymph nodes are biopsied at the time of surgery. Recognized involved nodes are removed at initial surgery, but selective node removal can be performed, and radical neck dissection is usually not required. This results in a decreased recurrence rate but has not been shown to improve survival. Follicular thyroid cancer commonly metastasizes to lungs and bone. When a remnant lobe remains, use of iodine I 131 as ablative therapy is compromised because the radioiodine will be preferentially taken up by the remnant normal tissue rather than by the tumor.
Radioactive iodine (RAI) therapy
Studies have shown that a postoperative course of therapeutic (ablative) doses of radioiodine 131I results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas. RAI may be given in addition to exogenous thyroid hormone but is not considered routine. RAI treatment is optimal after total thyroidectomy with minimal thyroid remnant. With a large thyroid remnant, a low thyroglobulin level cannot be achieved, which increases the chance of requiring multiple doses of RAI.
Consideration of RAI for remnant ablation is based on pathological risk features including the following:
RAI may be given with one of two methods of thyroid-stimulating hormone (TSH/thyrotropin) stimulation:
Administered rhTSH maintains quality of life and reduces the radiation dose delivered to the body compared with thyroid hormone withdrawal. Patients presenting with papillary thyroid microcarcinomas (tumors <10 mm), which are considered to be very low risk, have an excellent prognosis when treated surgically. Additional therapy with 131I would not be expected to improve the prognosis.
The role of RAI in low-risk patients is not clear because disease-free survival (DFS) or overall survival (OS) benefits have not been demonstrated.
Evidence (surgery with or without RAI):
Of the 1,298 patients, 911 patients received RAI after surgery, and 387 patients did not receive RAI after surgery. The follow-up period was 10.3 years.
Long-term complications of RAI using 131I include the following:
Options for reducing the amount of radiation exposure by reducing the amount of RAI in each dose and also giving RAI in combination with rhTSH injections have been explored for low-risk thyroid cancer patients.
Evidence (thyroid hormone withdrawal or use of rhTSH with 131I):
Neither study assessed the effect of low-dose RAI on long-term recurrences or survival. The studies also did not address whether RAI could be safely omitted in specific low-risk groups.
After thyroid surgery, all patients, except those undergoing lobectomy, will require thyroid hormone replacement therapy. For patients who have undergone thyroidectomy, supratherapeutic doses of thyroid hormone are routinely administered to suppress TSH levels. The degree of TSH suppression recommended depends on the risk of recurrence and the comorbidities of the patient. Studies have suggested that TSH suppression improves progression-free survival (PFS), but there is no definitive evidence that it improves OS.[18,19]
External-beam radiation therapy (EBRT)
EBRT is typically reserved for palliative treatment of unresectable or metastatic papillary or follicular thyroid cancer. In some cases, it may be appropriate to treat with EBRT in the adjuvant setting if there is confirmed or suspected microscopic residual disease that is confirmed or suspected to be refractory to RAI. There are no randomized trials to guide the selection of patients who might benefit from treatment with EBRT. The decision to use EBRT is based on retrospective data and clinical judgment.
Metastatic papillary and follicular thyroid cancer
Total thyroidectomy is still recommended as the initial treatment for metastatic papillary or follicular thyroid cancer. RAI is the second treatment and is given to ablate the remnant thyroid and treat the metastatic disease. If a thyroidectomy is not done, then RAI is not a treatment option for the patient. The most common sites of distant metastases are the lungs and bones. Treatment of distant metastases is usually not curative but may produce significant palliation. Standard treatment options for iodine-sensitive and iodine-resistant metastatic papillary and follicular thyroid cancer are described below.
Standard treatment options for iodine-sensitive thyroid cancer
Standard treatment options for iodine-sensitive thyroid cancer include the following:
Standard treatment options for iodine-resistant thyroid cancer
Standard treatment options for iodine-resistant thyroid cancer include the following:
TSH suppression with thyroxine is effective in many lesions that are not sensitive to 131I.
Sorafenib is an orally active, multityrosine kinase inhibitor.
Lenvatinib is an orally active, multitargeted tyrosine kinase inhibitor.
Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of 131I.
EBRT is considered for patients with localized lesions that are unresponsive to 131I.
Treatment options under clinical evaluation for metastatic papillary and follicular thyroid cancer
Patients unresponsive to 131I should also be considered candidates for clinical trials testing new approaches to this disease.
Recurrent papillary and follicular thyroid cancer
Approximately 10% to 30% of patients thought to be disease free after initial treatment will develop recurrence and/or metastases. Of these patients, approximately 80% develop recurrence with disease in the neck alone, and 20% develop recurrence with distant metastases. The most common site of distant metastasis is the lung. In a single series of 289 patients who developed recurrences after initial surgery, 16% died of cancer at a median time of 5 years after recurrence.
The prognosis for patients with clinically detectable recurrences is generally poor, regardless of cell type. Patients who recur with local or regional tumor detected only by 131I scan have a better prognosis.
The selection of further treatment depends on many factors, including the following:
Patients treated for differentiated thyroid cancer are followed carefully with physical examinations, serum quantitative thyroglobulin levels, and radiologic studies based on individual risk for recurrent disease.
Standard treatment options for recurrent papillary and follicular thyroid cancer
Standard treatment options for recurrent papillary and follicular thyroid cancer include the following:
Surgery with or without postoperative RAI therapy
Surgery with or without 131I ablation can be useful in controlling local recurrences, regional node metastases, or occasionally, metastases at other localized sites. Approximately 50% of the patients who undergo surgery for recurrent tumors can be rendered free of disease with a second operation. Local and regional recurrences detected by 131I scan and not clinically apparent can be treated with 131I ablation and have an excellent prognosis.
Up to 25% of recurrences and metastases from well-differentiated thyroid cancer may not show 131I uptake. For these patients, other standard imaging techniques such as ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scans may detect recurrent or metastatic disease.
Patients unresponsive to 131I should also be considered candidates for clinical trials testing new approaches to treating this disease.
Sorafenib is an orally active, multityrosine kinase inhibitor. It has been approved by the U.S. Food and Drug Administration as a treatment option when recurrent disease does not concentrate 131I or disease recurs after 131I ablation.
Lenvatinib is an orally active, multitargeted tyrosine kinase inhibitor.
EBRT or intraoperative radiation therapy can be useful in controlling symptoms related to local tumor recurrences.
Systemic chemotherapy can be considered. Chemotherapy has been reported to produce occasional objective responses, usually of short duration.[26,31]
Treatment options under clinical evaluation for recurrent papillary and follicular thyroid cancer
Clinical trials evaluating new treatment approaches to this disease should be considered for patients with recurrent papillary or follicular thyroid cancer. Oral inhibitors targeting specific activating point mutations are under clinical evaluation, as are new immunotherapy approaches.[27,28,29][Level of evidence: 2Dii]
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Sporadic and Hereditary MTC
MTC occurs in two forms, sporadic and hereditary. In the sporadic form, the tumor is usually unilateral. In the hereditary form, the tumor is almost always bilateral. In addition, the hereditary form may be associated with benign or malignant tumors of other endocrine organs, commonly referred to as the multiple endocrine neoplasia (MEN) syndromes types 2A and 2B (MEN2A or MEN2B). These syndromes are associated with pheochromocytoma of the adrenal gland and parathyroid hyperplasia.
Approximately 25% of reported cases of MTC are hereditary. Hereditary MTC syndromes include MEN2A, which is the most common, MEN2B, and hereditary non-MEN syndromes. (Refer to the PDQ summary on Genetics of Endocrine and Neuroendocrine Neoplasias for more information.) Any patient with an hereditary variant is screened for other associated endocrine tumors, particularly parathyroid hyperplasia and pheochromocytoma. Medullary carcinoma usually secretes calcitonin, a hormonal marker for the tumor, and may be detectable in blood even when the tumor is clinically occult. Determining the level of calcitonin is useful for diagnostic purposes and for following the results of treatment.
Patients with MTC (whether hereditary or sporadic) are tested for RET mutations, and if the mutations are positive, family members will also be tested. Family members may be screened for calcitonin elevation and for the RET proto-oncogene mutation to identify other individuals at risk for developing hereditary MTC. Because a modest elevation of calcitonin may lead to a false-positive diagnosis of medullary carcinoma, DNA testing for the RET mutation is the optimal approach. Family members who are gene carriers may choose to undergo prophylactic thyroidectomy at an early age.[1,2]
MTC comprises 3% to 4% of all thyroid cancers. These tumors usually present as a hard mass in the neck or thyroid, often associated with lymphadenopathy. MTC can also be diagnosed by fine-needle aspiration biopsy. Cytology typically reveals hypercellular tumors with spindle-shaped cells and poor adhesion. Metastases to regional lymph nodes are found in about 50% of the cases.
The overall survival rates of patients with MTC is 86% at 5 years and 65% at 10 years.
Prognosis depends on the following:
Poor prognostic factors include the following:[4,6,7]
Stage Information for MTC
Several staging systems have been employed to correlate extent of disease with long-term survival in MTC. The clinical staging system of the American Joint Committee on Cancer correlates survival to size of the primary tumor (T), presence or absence of lymph node involvement (N), and presence or absence of distant metastasis (M). Patients with the best prognosis are those who are diagnosed with the hereditary form of MTC after a positive screening for a RET mutation.
Standard Treatment Options for MTC
Standard treatment options for localized MTC include the following:
Radioactive iodine has no place in the treatment of patients with MTC.
Patients with MTC are treated with a total thyroidectomy unless there is evidence of distant metastasis. In patients with clinically palpable MTC, the incidence of microscopically positive nodes is more than 75%. Routine central and bilateral modified neck dissections are generally done. When cancer is confined to the thyroid gland, the prognosis is excellent.
EBRT has been used for palliation of locally recurrent tumors without evidence that it provides any survival advantage.
Locally advanced and metastatic disease
Standard treatment options for locally advanced and metastatic MTC include the following:
Vandetanib is an oral inhibitor of rearranged during transfection (RET) receptor kinase, vascular endothelial growth-factor receptor (VEGFR), and epidermal growth-factor receptor.
Cabozantinib is an oral tyrosine kinase inhibitor of RET receptor kinase, hepatocyte growth factor receptor MET, and VEGFR-2.
Palliative chemotherapy has been reported to produce occasional responses in patients with metastatic disease.[13,14,15,16] No single drug regimen can be considered standard. Some patients with distant metastases will experience prolonged survival and can be managed expectantly until they become symptomatic.
Undifferentiated (anaplastic) carcinoma is a highly malignant cancer of the thyroid. It grows rapidly and extends to structures beyond the thyroid. It typically presents as a hard, ill-defined mass, often with extension into the structures surrounding the thyroid. Anaplastic thyroid cancer must be carefully distinguished from lymphoma, which can have a similar presentation. This tumor usually occurs in an older age group and is characterized by extensive local invasion and rapid progression.
Five-year survival with this tumor is poor. Death is usually from uncontrolled local cancer in the neck, usually within months of diagnosis.
Stage Information for Anaplastic Thyroid Cancer
All patients with anaplastic thyroid cancer are considered to have stage IV disease.
Standard Treatment Options for Anaplastic Thyroid Cancer
Standard treatment options for anaplastic thyroid cancer include the following:
If the disease is confined to the local area, which is rare, total thyroidectomy is warranted to reduce symptoms caused by the tumor mass.[2,3] Tracheostomy is frequently necessary.
EBRT may be used in patients who are not surgical candidates or whose tumor cannot be surgically excised.
Anaplastic thyroid cancer is not responsive to iodine I 131 therapy. Treatment with individual anticancer drugs has been reported to produce partial remissions in some patients. Approximately 30% of patients achieve a partial remission with doxorubicin. The combination of doxorubicin plus cisplatin appears to be more active than doxorubicin alone and has been reported to produce more complete responses.
The combination of chemotherapy plus radiation therapy in patients after complete resection may provide prolonged survival but has not been compared with any one modality alone.[6,7]
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment Option Overview for Thyroid Cancer
Editorial changes were made to this section.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult thyroid cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Thyroid Cancer Treatment (Adult) are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Thyroid Cancer Treatment (Adult). Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389164]
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Last Revised: 2018-08-14
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