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NCI/PDQ® Health professionals: Thyroid Cancer Treatment (PDQ®)
National Cancer Institute
Last Modified: May 9, 2012

TABLE OF CONTENTS


General Information About Thyroid Cancer

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Incidence and Mortality

Estimated new cases and deaths from thyroid cancer in the United States in 2012: 1

  • New cases: 56,460.
  • Deaths: 1,780.

Carcinoma of the thyroid gland is an uncommon cancer but is the most common malignancy of the endocrine system. 2 Differentiated tumors (papillary or follicular) are highly treatable and usually curable. Poorly differentiated tumors (medullary or anaplastic) are much less common, are aggressive, metastasize early, and have a much poorer prognosis. Thyroid cancer affects women more often than men and usually occurs in people between the ages of 25 and 65 years. The incidence of this malignancy has been increasing over the last decade. Thyroid cancer commonly presents as a cold nodule. 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


Risk Factors

Patients with a history of radiation administered in infancy and childhood for benign conditions of the head and neck, such as enlarged thymus, acne, or tonsillar or adenoidal enlargement, have an increased risk of cancer as well as other abnormalities of the thyroid gland. In this group of patients, malignancies of the thyroid gland first appear beginning as early as 5 years following radiation and may appear 20 or more years later. 5 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 the development of thyroid cancer include the following: 9

  • A history of goiter.
  • Family history of thyroid disease.
  • Female gender.
  • Asian race.


Prognostic Factors

The prognosis for differentiated carcinoma is better for patients younger than 40 years without extracapsular extension or vascular invasion. 10 11 12 13 14 Age appears to be the single most important prognostic factor. 12 The prognostic significance of lymph node status is controversial. One retrospective surgical series of 931 previously untreated patients with differentiated thyroid cancer found that female gender, multifocality, and regional node involvement are favorable prognostic factors. 15 Adverse factors included age older than 45 years, follicular histology, primary tumor larger than 4 cm (T2T3), extrathyroid extension (T4), and distant metastases. 15 16 Other studies, however, have shown that regional lymph node involvement had no effect 17 18 or even an adverse effect on survival. 13 14 19

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. 20 An elevated serum thyroglobulin level correlates strongly with recurrent tumor when found in patients with differentiated thyroid cancer during postoperative evaluations. 21 22 Serum thyroglobulin levels are most sensitive when patients are hypothyroid and have elevated serum thyroid-stimulating hormone levels. 23 Expression of the tumor suppressor gene p53 has also been associated with an adverse prognosis for patients with thyroid cancer. 24

Patients considered at low risk by the age, metastases, extent, and size (AMES) risk criteria include women younger than 50 years and men younger than 40 years without evidence of distant metastases. Also included in the low-risk group are older patients with primary tumors smaller than 5 cm and papillary cancer without evidence of gross extrathyroid invasion or follicular cancer without either major capsular invasion or blood vessel invasion. 11 Using these criteria, a retrospective study of 1,019 patients showed that the 20-year survival rate is 98% for low-risk patients and 50% for high-risk patients. 11 The 10-year overall relative survival rates for patients in the United States are 93% for papillary cancer, 85% for follicular cancer, 75% for medullary cancer, and 14% for undifferentiated/anaplastic cancer. 2

The thyroid gland may occasionally be the site of other primary tumors, including sarcomas, lymphomas, epidermoid carcinomas, and teratomas and may be the site of metastasis from other cancers, particularly of the lung, breast, and kidney.


Related Summaries

Other PDQ® summaries containing information related to thyroid cancer include the following:

References:

  1. American Cancer Society.: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. Available online [PUBMED Abstract]
  2. Hundahl SA, Fleming ID, Fremgen AM, et al.: A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments] Cancer 83 (12): 2638-48, 1998. [PUBMED Abstract]
  3. Tennvall J, Biírklund A, Míller T, et al.: Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid carcinoma? Retrospective multivariate analysis of differentiated thyroid carcinoma with long follow-up. Cancer 57 (7): 1405-14, 1986. [PUBMED Abstract]
  4. Khoo ML, Asa SL, Witterick IJ, et al.: Thyroid calcification and its association with thyroid carcinoma. Head Neck 24 (7): 651-5, 2002. [PUBMED Abstract]
  5. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72. [PUBMED Abstract]
  6. Pacini F, Vorontsova T, Molinaro E, et al.: Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 352 (9130): 763-6, 1998. [PUBMED Abstract]
  7. Cardis E, Kesminiene A, Ivanov V, et al.: Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst 97 (10): 724-32, 2005. [PUBMED Abstract]
  8. Tronko MD, Howe GR, Bogdanova TI, et al.: A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening. J Natl Cancer Inst 98 (13): 897-903, 2006. [PUBMED Abstract]
  9. Iribarren C, Haselkorn T, Tekawa IS, et al.: Cohort study of thyroid cancer in a San Francisco Bay area population. Int J Cancer 93 (5): 745-50, 2001. [PUBMED Abstract]
  10. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988. [PUBMED Abstract]
  11. Sanders LE, Cady B: Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133 (4): 419-25, 1998. [PUBMED Abstract]
  12. Mazzaferri EL: Treating differentiated thyroid carcinoma: where do we draw the line? Mayo Clin Proc 66 (1): 105-11, 1991. [PUBMED Abstract]
  13. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994. [PUBMED Abstract]
  14. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [PUBMED Abstract]
  15. Shah JP, Loree TR, Dharker D, et al.: Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164 (6): 658-61, 1992. [PUBMED Abstract]
  16. Andersen PE, Kinsella J, Loree TR, et al.: Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 170 (5): 467-70, 1995. [PUBMED Abstract]
  17. Coburn MC, Wanebo HJ: Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. Am J Surg 164 (6): 671-6, 1992. [PUBMED Abstract]
  18. Voutilainen PE, Multanen MM, Leppíniemi AK, et al.: Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11 (10): 953-7, 2001. [PUBMED Abstract]
  19. Sellers M, Beenken S, Blankenship A, et al.: Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. Am J Surg 164 (6): 578-81, 1992. [PUBMED Abstract]
  20. Lennard CM, Patel A, Wilson J, et al.: Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129 (5): 552-8, 2001. [PUBMED Abstract]
  21. van Herle AJ, van Herle KA: Thyroglobulin in benign and malignant thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 601-618. [PUBMED Abstract]
  22. Ruiz-Garcia J, Ruiz de Almodóvar JM, Olea N, et al.: Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. J Nucl Med 32 (3): 395-8, 1991. [PUBMED Abstract]
  23. Duren M, Siperstein AE, Shen W, et al.: Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients. Surgery 126 (1): 13-9, 1999. [PUBMED Abstract]
  24. Godballe C, Asschenfeldt P, Jírgensen KE, et al.: Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108 (2): 243-9, 1998. [PUBMED Abstract]


Cellular Classification of Thyroid Cancer

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Cell type is an important determinant of prognosis in thyroid cancer. There are four main varieties of thyroid cancer (although, for clinical management of the patient, thyroid cancer is generally divided into two categories: well differentiated or poorly differentiated): 1

  • Papillary carcinoma.
    • Papillary/follicular carcinoma.

  • Follicular carcinoma.
    • Hí¼rthle cell carcinoma, a variant of follicular carcinoma with a poorer prognosis. 2 3

  • Medullary carcinoma.
  • Anaplastic carcinoma.
    • Small cell carcinoma.
    • Giant cell carcinoma.

  • Others.
    • Lymphoma.
    • Sarcoma.
    • Carcinosarcoma.

A definition for each major type can be found under stage information.

References:

  1. LiVolsi VA: Pathology of thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 127-175. [PUBMED Abstract]
  2. Kushchayeva Y, Duh QY, Kebebew E, et al.: Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 195 (4): 457-62, 2008. [PUBMED Abstract]
  3. Mills SC, Haq M, Smellie WJ, et al.: Hí¼rthle cell carcinoma of the thyroid: Retrospective review of 62 patients treated at the Royal Marsden Hospital between 1946 and 2003. Eur J Surg Oncol 35 (3): 230-4, 2009. [PUBMED Abstract]


Stage Information for Thyroid Cancer

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Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define thyroid cancer. 1


Table 1. Primary Tumor (T)a,b

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.bAll categories may be subdivided: (s) solitary tumor and (m) multifocal tumor (the largest determines the classification).cAll anaplastic carcinomas are considered T4 tumors.
TX  Primary tumor cannot be assessed. 
T0  No evidence of primary tumor. 
T1  Tumor 2 cm in greatest dimension limited to the thyroid. 
T1a  Tumor 1 cm, limited to the thyroid. 
T1b  Tumor >1 cm but 2 cm in greatest dimension, limited to the thyroid. 
T2  Tumor >2 cm but 4 cm in greatest dimension, limited to the thyroid. 
T3  Tumor >4 cm in greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). 
T4a  Moderately advanced disease. 
Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve. 
T4b  Very advanced disease. 
Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels. 
cT4a  Intrathyroidal anaplastic carcinoma. 
cT4b  Anaplastic carcinoma with gross extrathyroid extension. 
 
 
 


Table 2. Regional Lymph Nodes (N)a,b

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.bRegional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes.
NX  Regional lymph nodes cannot be assessed. 
N0  No regional lymph node metastasis. 
N1  Regional lymph node metastasis. 
N1a  Metastases to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes). 
N1b  Metastases to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII). 
 
 


Table 3. Distant Metastasis (M)a

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.
M0  No distant metastasis. 
M1  Distant metastasis. 
 


Table 4. Anatomic Stage/Prognostic Groupsa,b

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.bSeparate stage groupings are recommended for papillary or follicular (differentiated), medullary, and anaplastic (undifferentiated) carcinoma.cAll anaplastic carcinomas are considered Stage IV.
Stage  T  N  M 
Papillary or follicular (differentiated) 
YOUNGER THAN 45 YEARS 
I  Any T  Any N  M0 
II  Any T  Any N  M1 
45 YEARS AND OLDER 
I  T1  N0  M0 
II  T2  N0  M0 
III  T3  N0  M0 
  T1  N1a  M0 
  T2  N1a  M0 
  T3  N1a  M0 
IVA  T4a  N0  M0 
  T4a  N1a  M0 
  T1  N1b  M0 
  T2  N1b  M0 
  T3  N1b  M0 
  T4a  N1b  M0 
IVB  T4b  Any N  M0 
Stage IVC  Any T  Any N  M1 
Medullary carcinoma (all age groups) 
I  T1  N0  M0 
II  T2  N0  M0 
  T3  N0  M0 
III  T1  N1a  M0 
  T1  N1a  M0 
  T2  N1a  M0 
  T3  N1a  M0 
IVA  T4a  N0  M0 
  T4a  N1a  M0 
  T1  N1b  M0 
  T2  N1b  M0 
  T3  N1b  M0 
  T4a  N1b  M0 
  Stage IVB  T4b  Any N 
IVB  T4b  Any N  M0 
IVC  Any T  Any N  M1 
Anaplastic carcinomac 
IVA  T4a  Any N  M0 
IVB  T4b  Any N  M0 
IVC  Any T  Any N  M1 
 
 
 


Papillary and Follicular Thyroid Cancer

Stage I papillary thyroid cancer

Stage I papillary carcinoma is localized to the thyroid gland. In as many as 50% of cases, there are multifocal sites of papillary adenocarcinomas throughout the gland. Most papillary cancers have some follicular elements, and these may sometimes be more numerous than the papillary formations, but this does not change the prognosis. The 10-year survival rate is slightly better for patients younger than 45 years than for patients older than 45 years.

Stage II papillary thyroid cancer

Stage II papillary carcinoma is defined as either: (1) tumor that has spread distantly in patients younger than 45 years, or (2) tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older than 45 years. In as many as 50% to 80% of cases, there are multifocal sites of papillary adenocarcinomas throughout the gland. Most papillary cancers have some follicular elements, and these may sometimes be more numerous than the papillary formations, but this does not appear to change the prognosis.

Stage III papillary thyroid cancer

Stage III is papillary carcinoma in patients older than 45 years that is larger than 4 cm and is limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Papillary carcinoma that has invaded adjacent cervical tissue has a worse prognosis than tumors confined to the thyroid.

Stage IV papillary thyroid cancer

Stage IV is papillary carcinoma in patients older than 45 years with extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent distant sites of spread, though such distant spread is rare in this type of thyroid cancer. Papillary carcinoma more frequently metastasizes to regional lymph nodes than to distant sites. The prognosis for patients with distant metastases is poor.

Stage I follicular thyroid cancer

Stage I follicular carcinoma is localized to the thyroid gland. Follicular thyroid carcinoma must be distinguished from follicular adenomas, which are characterized by their lack of invasion through the capsule into the surrounding thyroid tissue. 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.

Stage II follicular thyroid cancer

Stage II follicular carcinoma is defined as either tumor that has spread distantly in patients younger than 45 years, or tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older than 45 years. The presence of lymph node metastases does not worsen the prognosis among patients younger than 45 years. Follicular thyroid carcinoma must be distinguished from follicular adenomas, which are characterized by their lack of invasion through the capsule into the surrounding thyroid tissue. 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 for patients with vascular invasion.

Stage III follicular thyroid cancer

Stage III is follicular carcinoma in patients older than 45 years, larger than 4 cm and limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Follicular carcinoma invading cervical tissue has a worse prognosis than tumors confined to the thyroid gland. The presence of vascular invasion is an additional poor prognostic factor. Metastases to lymph nodes do not worsen the prognosis in patients younger than 45 years.

Stage IV follicular thyroid cancer

Stage IV is follicular carcinoma in patients older than 45 years with extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent sites of spread. Follicular carcinomas more commonly have blood vessel invasion and tend to metastasize hematogenously to the lungs and to the bone rather than through the lymphatic system. The prognosis for patients with distant metastases is poor.

Hí¼rthle cell carcinoma

Hí¼rthle cell carcinoma is a variant of follicular carcinoma with a similar prognosis and should be treated in the same way as equivalent stage non-Hí¼rthle cell follicular carcinoma. 2


Medullary Thyroid Cancer

Several staging systems have been employed to correlate extent of disease with long-term survival in medullary thyroid cancer. The clinical staging system of the AJCC correlates survival to size of the primary tumor, presence or absence of lymph node metastases, and presence or absence of distance metastasis. Patients with the best prognosis are those who are diagnosed by provocative screening, prior to the appearance of palpable disease. 3

Stage 0 medullary thyroid cancer

Clinically occult disease detected by provocative biochemical screening.

Stage I medullary thyroid cancer

Tumor smaller than 2 cm.

Stage II medullary thyroid cancer

Tumor larger than 2 cm but 4 cm or smaller with no metastases or larger than 4 cm with minimal extrathyroid extension.

Stage III medullary thyroid cancer

Tumor of any size with metastases limited to the pretracheal, paratracheal, or prelaryngeal/Delphian lymph nodes.

Stage IV medullary thyroid cancer

Stage IV medullary thyroid cancer is divided into the following categories:

  • Stage IVA (moderately advanced with or without lymph node metastases [for T4a] but without distant metastases).
  • Stage IVB (very advanced with or without lymph node metastases but no distant metastases).
  • Stage IVC (distant metastases).

Medullary carcinoma usually presents as a hard mass and is often accompanied by blood vessel invasion. Medullary thyroid cancer occurs in two forms, sporadic and familial. In the sporadic form, the tumor is usually unilateral. In the familial form, the tumor is almost always bilateral. In addition, the familial form may be associated with benign or malignant tumors of other endocrine organs, commonly referred to as the multiple endocrine neoplasia syndromes (MEN 2A or MEN 2B).

In these syndromes, there is an association with pheochromocytoma of the adrenal gland and parathyroid hyperplasia. Medullary carcinoma usually secretes calcitonin, a hormonal marker for the tumor, and may be detectable in blood even when the tumor is clinically occult. Metastases to regional lymph nodes are found in about 50% of cases. Prognosis depends on extent of disease at presentation, presence or absence of regional lymph node metastases, and completeness of the surgical resection. 4

Family members should be screened for calcitonin elevation to identify individuals who are at risk of developing familial medullary thyroid cancer. MEN 2A gene carrier status can be more accurately determined by analysis of mutations in the RET gene. Whereas modest elevation of calcitonin may lead to a false-positive diagnosis of medullary carcinoma, DNA testing for the RET mutation is the optimal approach in evaluating MEN 2A. All patients with medullary carcinoma of the thyroid (whether familial or sporadic) should be tested for RET mutations, and, if they are positive, family members should also be tested. Family members who are gene carriers should undergo prophylactic thyroidectomy at an early age. 5 6 7


Anaplastic Thyroid Cancer

No generally accepted staging system is available for anaplastic thyroid cancer. All patients are considered to have stage IV disease.

Undifferentiated (anaplastic) carcinomas are highly malignant cancers of the thyroid. They may be subclassified as small cell or large cell carcinomas. Both grow rapidly and extend to structures beyond the thyroid. Both small cell and large cell carcinomas present as hard, ill-defined masses, often with extension into the structures surrounding the thyroid. Small cell anaplastic thyroid carcinoma must be carefully distinguished from lymphoma. 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. 8

References:

  1. Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96. [PUBMED Abstract]
  2. Haigh PI, Urbach DR: The treatment and prognosis of Hí¼rthle cell follicular thyroid carcinoma compared with its non-Hí¼rthle cell counterpart. Surgery 138 (6): 1152-7; discussion 1157-8, 2005. [PUBMED Abstract]
  3. Colson YL, Carty SE: Medullary thyroid carcinoma. Am J Otolaryngol 14 (2): 73-81, 1993 Mar-Apr. [PUBMED Abstract]
  4. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72. [PUBMED Abstract]
  5. Lips CJ, Landsvater RM, Híppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331 (13): 828-35, 1994. [PUBMED Abstract]
  6. Decker RA, Peacock ML, Borst MJ, et al.: Progress in genetic screening of multiple endocrine neoplasia type 2A: is calcitonin testing obsolete? Surgery 118 (2): 257-63; discussion 263-4, 1995. [PUBMED Abstract]
  7. Skinner MA, Moley JA, Dilley WG, et al.: Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353 (11): 1105-13, 2005. [PUBMED Abstract]
  8. Neff RL, Farrar WB, Kloos RT, et al.: Anaplastic thyroid cancer. Endocrinol Metab Clin North Am 37 (2): 525-38, xi, 2008. [PUBMED Abstract]


Stage I and II Papillary and Follicular Thyroid Cancer

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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 may be similar; the difference between them lies in the rates of surgical complications and local recurrences. 1 2 3 4 5 6 7

Standard treatment options:

  1. Total thyroidectomy: This procedure is advocated 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. The procedure is associated with a higher incidence of hypoparathyroidism, but this complication may be reduced when a small amount of tissue remains on the contralateral side. This approach facilitates follow-up thyroid scanning.

    I131:: Studies have shown that a postoperative course of therapeutic Studies have shown that a postoperative course of therapeutic (ablative) doses of I(ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas.and follicular carcinomas. 4 It may be given in addition to exogenous thyroid It may be given in addition to exogenous thyroid hormone but is not considered routine.hormone but is not considered routine. 8 Patients presenting with papillary Patients presenting with papillary thyroid microcarcinomas (tumors thyroid microcarcinomas (tumors <<10 mm) have an excellent prognosis when 10 mm) have an excellent prognosis when treated surgically, and additional therapy with Itreated surgically, and additional therapy with I131 would not be expected to would not be expected to improve the prognosis.improve the prognosis. 9

  2. Lobectomy: This procedure is associated with a lower incidence of complications, but approximately 5% to 10% of patients will have a recurrence in the thyroid following lobectomy. 10 Patients younger than 45 years will have the longest follow-up period and the greatest opportunity for recurrence. Follicular thyroid cancer commonly metastasizes to lungs and bone; with a remnant lobe in place, use of I131 as ablative therapy is compromised. Abnormal regional lymph nodes should be biopsied at the time of surgery. Recognized nodal involvement should be 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.

    Following the surgical procedure, patients should receive postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress thyroid-stimulating hormone (TSH); studies have shown a decreased incidence of recurrence when TSH is suppressed.

    I131:: Studies have shown that a postoperative course of therapeutic Studies have shown that a postoperative course of therapeutic (ablative) doses of I(ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas.and follicular carcinomas. 4 It may be given in addition to exogenous thyroid It may be given in addition to exogenous thyroid hormone but is not considered routine.hormone but is not considered routine. 8 Patients presenting with papillary Patients presenting with papillary thyroid microcarcinomas (tumors thyroid microcarcinomas (tumors <<10 mm) have an excellent prognosis when 10 mm) have an excellent prognosis when treated surgically, and additional therapy with Itreated surgically, and additional therapy with I131 would not be expected to would not be expected to improve the prognosis.improve the prognosis. 9


Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I papillary thyroid cancer, stage I follicular thyroid cancer, stage II papillary thyroid cancer and stage II follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72. [PUBMED Abstract]
  2. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988. [PUBMED Abstract]
  3. Cady B, Rossi R: An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 104 (6): 947-53, 1988. [PUBMED Abstract]
  4. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [PUBMED Abstract]
  5. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994. [PUBMED Abstract]
  6. Tollefsen HR, Shah JP, Huvos AG: Follicular carcinoma of the thyroid. Am J Surg 126 (4): 523-8, 1973. [PUBMED Abstract]
  7. Edis AJ: Surgical treatment for thyroid cancer. Surg Clin North Am 57 (3): 533-42, 1977. [PUBMED Abstract]
  8. Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984. [PUBMED Abstract]
  9. Hay ID, Grant CS, van Heerden JA, et al.: Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 112 (6): 1139-46; discussion 1146-7, 1992. [PUBMED Abstract]
  10. Hay ID, Grant CS, Bergstralh EJ, et al.: Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124 (6): 958-64; discussion 964-6, 1998. [PUBMED Abstract]


Stage III Papillary and Follicular Thyroid Cancer

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Standard treatment options:

  1. Total thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease.
  2. I131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope. 1
  3. External-beam radiation therapy if I131 uptake is minimal. 2


Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III papillary thyroid cancer and stage III follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984. [PUBMED Abstract]
  2. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978. [PUBMED Abstract]


Stage IV Papillary and Follicular Thyroid Cancer

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The most common sites of metastases are lymph nodes, lung, and bone. Treatment of lymph node metastases alone is often curative. Treatment of distant metastases is usually not curative but may produce significant palliation.

Standard treatment options:

  1. I131: Metastases that demonstrate uptake of this isotope may be ablated by therapeutic doses of I131.
  2. External-beam radiation therapy for patients with localized lesions that are unresponsive to I131. 1
  3. Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of I131.
  4. Thyroid-stimulating hormone suppression with thyroxine is also effective in many lesions not sensitive to I131.

Patients unresponsive to I131 should also be considered candidates for clinical trials testing new approaches to this disease.

Treatment options under clinical evaluation:

  • Clinical trials evaluating new treatment approaches to this disease should also be considered for these patients. Chemotherapy has been reported to produce occasional complete responses of long duration. 2 3 4 Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation. 5[Level of evidence: 2Dii]


Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV papillary thyroid cancer and stage IV follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978. [PUBMED Abstract]
  2. Gottlieb JA, Hill CS Jr, Ibanez ML, et al.: Chemotherapy of thyroid cancer. An evaluation of experience with 37 patients. Cancer 30 (3): 848-53, 1972. [PUBMED Abstract]
  3. Harada T, Nishikawa Y, Suzuki T, et al.: Bleomycin treatment for cancer of the thyroid. Am J Surg 122 (1): 53-7, 1971. [PUBMED Abstract]
  4. Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985. [PUBMED Abstract]
  5. Sherman SI, Wirth LJ, Droz JP, et al.: Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359 (1): 31-42, 2008. [PUBMED Abstract]


Medullary Thyroid Cancer

Back Up

Medullary thyroid cancer (MTC) comprises 3% to 4% of all thyroid cancers. These tumors usually present as a mass in the neck or thyroid, often associated with lymphadenopathy, 1 or they may be diagnosed through screening family members. MTC can also be diagnosed by fine-needle aspiration biopsy. Cytology typically reveals hypercellular tumors with spindle-shaped cells and poor adhesion. 2

The overall survival of patients with MTC is 86% at 5 years and 65% at 10 years. Poor prognostic factors include advanced age, advanced stage, prior neck surgery, and associated multiple endocrine neoplasia (MEN) 2B. 2 3 4

Approximately 25% of reported cases of MTC are familial. Familial MTC syndromes include MEN 2A, which is the most common; MEN 2B; and familial non-MEN syndromes. (Refer to the PDQ® summary on Genetics of Medullary Thyroid Cancer for more information.) Any patient with a familial variant should be screened for other associated endocrine tumors, particularly parathyroid hyperplasia and pheochromocytoma. MTC can secrete calcitonin and other peptide substances. Determining the level of calcitonin is useful for diagnostic purposes and for following the results of treatment.

Family members should be screened for calcitonin elevation and/or for the RET proto-oncogene mutation to identify other individuals at risk for developing familial MTC. All patients with MTC (whether familial or sporadic) should be tested for RET mutations, and if they are positive, family members should also be tested. Whereas 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 should undergo prophylactic thyroidectomy at an early age. 5 6

Treatment options for localized disease:

  1. Thyroidectomy: Patients with medullary thyroid cancer should be treated with a total thyroidectomy, unless there is evidence of distant metastasis. In patients with clinically palpable medullary carcinoma of the thyroid, the incidence of microscopically positive nodes is more than 75%; routine central and bilateral modified neck dissections have been recommended. 7 When cancer is confined to the thyroid gland, the prognosis is excellent.
  2. External radiation therapy: External radiation therapy has been used for palliation of locally recurrent tumors, without evidence that it provides any survival advantage. 8 Radioactive iodine has no place in the treatment of patients with MTC.

Treatment options for locally advanced and metastatic disease:

  • Palliative chemotherapy: Vandetanib is an oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling. It was tested in a placebo-controlled prospective trial (NCT00410761) in 331 patients with locally advanced and metastatic disease with a 2:1 ratio in assignment to the study drug.

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