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Thyroid Cancer Treatment Information
for Physicians

Important: This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Table of Contents

 

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
Stage I papillary
Stage II papillary
Stage III papillary
Stage IV papillary
Stage I follicular
Stage II follicular
Stage III follicular
Stage IV follicular
Medullary
Anaplastic
TREATMENT OPTION OVERVIEW
STAGE I PAPILLARY THYROID CANCER
STAGE I FOLLICULAR THYROID CANCER
STAGE II PAPILLARY THYROID CANCER
STAGE II FOLLICULAR THYROID CANCER
STAGE III PAPILLARY THYROID CANCER
STAGE III FOLLICULAR THYROID CANCER
STAGE IV PAPILLARY THYROID CANCER
STAGE IV FOLLICULAR THYROID CANCER
MEDULLARY THYROID CANCER
ANAPLASTIC THYROID CANCER
RECURRENT THYROID CANCER

GENERAL INFORMATION

Carcinoma of the thyroid gland is an uncommon cancer but, nonetheless, is the most common malignancy of the endocrine system. Differentiated tumors (papillary or follicular) are highly treatable and usually curable. Poorly differentiated cancers (medullary or anaplastic) are much less common, are aggressive, metastasize early, and have a much poorer prognosis. Thyroid cancer affects women more commonly than men, and the majority of cases occur in patients between the ages of 25 and 65. The incidence of this malignancy has been increasing over the last decade. The prognosis for differentiated carcinoma is better for patients younger than 40 years of age without extracapsular extension or vascular invasion.[1-5] Age appears to be the single most important prognostic factor.[3] 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 patients under 40 years of age.[6]

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.[7] Adverse factors included age over 45 years, follicular histology, primary greater than 4 centimeters (T2-3), extrathyroid extension (T4), and distant metastases.[7,8] Other studies, however, have shown that regional lymph node involvement had no effect [9] or even an adverse effect on survival.[4,5,10] An elevated serum thyroglobulin level correlates strongly with recurrent tumor when found in patients with differentiated thyroid cancer during postoperative evaluations.[11,12] Expression of the tumor suppressor gene p53 has also been associated with an adverse prognosis for patients with thyroid cancer.[13]

Patients considered to be low-risk by the age, metastases, extent, and size (AMES) risk criteria include women younger than 50 years of age and men younger than 40 years of age without evidence of distant metastases. Also included in the low-risk group are older patients with primary tumors less than 5 centimeters and papillary cancer without evidence of gross extrathyroid invasion or follicular cancer without either major capsular invasion or blood vessel invasion.[2] Using these criteria, a retrospective study of 1019 patients showed that the 20-year survival rate is 98% for low-risk patients and 50% for high-risk patients.[2]

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

References:

  1. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: Is extent of surgical resection important? Surgery 104(6): 954-962, 1988.
  2. Sanders LE, Cady B: Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Archives of Surgery 133(4): 419-425, 1998.
  3. Mazzaferri EL: Treating differentiated thyroid carcinoma: where do we draw the line? Mayo Clinic Proceedings 66(1): 105-111, 1991.
  4. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. European Journal of Surgical Oncology 20: 613-621, 1994.
  5. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. American Journal of Medicine 97: 418-428, 1994.
  6. Tennvall J, Biorklund A, Moller 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): 1405-1414, 1986.
  7. Shah JP, Loree TR, Dharker D, et al.: Prognostic factors in differentiated carcinoma of the thyroid gland. American Journal of Surgery 164(6): 658-661, 1992.
  8. Andersen PE, Kinsella J, Loree TR, et al.: Differentiated carcinoma of the thyroid with extrathyroidal extension. American Journal of Surgery 170(5): 467-470, 1995.
  9. Coburn MC, Wanebo HJ: Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. American Journal of Surgery 164(6): 671-676, 1992.
  10. Sellers M, Beenken S, Blankenship A, et al.: Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. American Journal of Surgery 164(6): 578-581, 1992.
  11. van Herle AJ, Brown DG: Thyroglobulin in benign and malignant thyroid disease. In: Falk SA: Thyroid disease: endocrinology, surgery, nuclear medicine, and radiotherapy. New York: Raven Press, 1990, pp 473-484.
  12. Ruiz-Garcia J, Ruiz de Almodovar JM, Olea N, et al.: Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. Journal of Nuclear Medicine 32(3): 395-398, 1991.
  13. Godballe C, Asschenfeldt P, Jorgensen KE, et al.: Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108(2): 243-249, 1998.
  14. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1629-1652.

CELLULAR CLASSIFICATION

Cell type is an important determinant of prognosis in thyroid cancer. There are 4 main varieties of thyroid cancer (although, for clinical management of the patient, thyroid cancer is generally divided into well-differentiated or poorly differentiated):[1]

a) papillary carcinoma
papillary/follicular carcinoma


b) follicular carcinoma

Hurthle cell carcinoma


c) medullary carcinoma

d) anaplastic carcinoma

small cell carcinoma
giant cell carcinoma


e) 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. New York: Raven Press, 1990, pp 127-175.

STAGE INFORMATION

The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification.[1]

-- TNM definitions --
Primary tumor (T)
Note:  All categories may be subdivided into (a) solitary tumor or (b)
multifocal tumor (the largest determines the classification)
     TX:  Primary tumor cannot be assessed
     T0:  No evidence of primary tumor
     T1:  Tumor 1 cm or less in greatest dimension limited to the thyroid
     T2:  Tumor more than 1 cm but not more than 4 cm in greatest dimension
          limited to the thyroid
     T3:  Tumor more than 4 cm in greatest dimension limited to the thyroid
     T4:  Tumor of any size extending beyond the thyroid capsule

Regional lymph nodes (N)
Regional lymph nodes are the 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:  Metastasis in ipsilateral cervical lymph node(s)
          N1b:  Metastasis in bilateral, midline, or contralateral cervical or
                mediastinal lymph node(s)

Distant metastases (M)
     MX:  Distant metastasis cannot be assessed
     M0:  No distant metastasis
     M1:  Distant metastasis

-- AJCC stage groupings --
Papillary or follicular
  Under 45 years
     Stage I:  Any T, Any N, M0
     Stage II:  Any T, Any N, M1
  45 years and older
     Stage I:  T1, N0, M0
     Stage II:  T2, N0, M0
                T3, N0, M0
     Stage III:  T4, N0, M0
                 Any T, N1, M0
     Stage IV:  Any T, Any N, M1

Medullary
     Stage I:  T1, N0, M0
     Stage II:  T2, N0, M0
                T3, N0, M0
                T4, N0, M0
     Stage III:  Any T, N1, M0
     Stage IV:  Any T, Any N, M1

Undifferentiated (anaplastic)
  All cases are stage IV
     Stage IV:  Any T, Any N, Any M
Stage I papillary

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 40 years of age than for patients older than 40 years of age.

Stage II papillary

Stage II papillary carcinoma is defined as either 1) tumor that has spread distantly in patients younger than 45 years of age or 2) tumor that is greater than 1 centimeter in size and is limited to the thyroid gland in patients older than 45 years of age. 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

Stage III is papillary carcinoma in patients older than 45 years of age with local cervical invasion or positive lymph nodes. Papillary carcinoma which has invaded adjacent cervical tissue has a worse prognosis than tumors confined to the thyroid.

Stage IV papillary

Stage IV is papillary carcinoma in patients older than 45 years of age with distant metastases. The lungs and bone are the most frequent distant sites of spread, although 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

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 cancers have a good prognosis, it is less favorable than that of papillary carcinoma. The 10-year survival for patients with follicular carcinoma without vascular invasion is better than for patients with vascular invasion.

Stage II follicular

Stage II follicular carcinoma is defined as either; tumor that has spread distantly in patients younger than 45 years of age, or tumor that is greater than 1 centimeter in size and is limited to the thyroid gland in patients older than 45 years of age. The presence of lymph node metastases does not worsen the prognosis. 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 cancers have a good prognosis, it is less favorable than that of papillary carcinoma; the 10-year survival for patients with follicular carcinoma without vascular invasion is better than for patients with vascular invasion.

Stage III follicular

Stage III is follicular carcinoma in patients older than 45 years of age with local cervical invasion or positive lymph 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.

Stage IV follicular

Stage IV is follicular carcinoma in patients older than 45 years of age with 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.

Medullary

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.[2]

Stage I medullary
Tumor less than 1 cm in size or clinically occult disease detected by provocative biochemical screening

Stage II medullary
Tumor greater than 1 cm but less than 4 cm

Stage III medullary
Lymph node metastasis

Stage IV medullary
Distant metastasis (any T, any N, M1)

Medullary carcinoma usually presents as a hard mass, and is often accompanied by blood vessel invasion. Medullary thyroid cancer occurs in 2 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 this syndrome, 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 though 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.[3]

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, then family members should also be tested. Family members who are gene carriers should undergo prophylactic thyroidectomy at an early age.[4,5]

Anaplastic

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

Undifferentiated (anaplastic) carcinoma tumors 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 carcinoma 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.

References:

  1. Thyroid Gland. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 59-64.
  2. Colson YL, Carty SE: Medullary thyroid carcinoma. American Journal of Otolaryngology 14(2): 73-81, 1993.
  3. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1629-1652.
  4. Lips CJ, Landsvater RM, Hoppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. New England Journal of Medicine 331(13): 828-835, 1994.
  5. 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): 257-264, 1995.

TREATMENT OPTION OVERVIEW

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.

STAGE I PAPILLARY 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 may be similar; the difference between them lies in the rates of surgical complications and local recurrences.[1-5]

Treatment options:

Standard:

1. 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.[6] Patients younger than 45 years of age will have the longest follow-up period and the greatest opportunity for recurrence. 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 not required.

Following the surgical procedure, patients should receive postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress TSH, since studies have shown a decreased incidence of recurrence.

I-131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I-131 results in a decreased recurrence rate in papillary and follicular carcinomas.[4] It may be given in addition to exogenous thyroid hormone, but is not considered routine.[7] Patients presenting with papillary thyroid microcarcinomas (tumors <10 mm) have an excellent prognosis when treated surgically, and additional therapy with I-131 would not be expected to improve the prognosis.[8]

2. Total thyroidectomy: This procedure is advocated because of the high incidence of multicentric involvement of both lobes of the gland and the question of de-differentiation of the 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.

References:
  1. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1629-1652.
  2. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: Is extent of surgical resection important? Surgery 104(6): 954-962, 1988.
  3. Cady B, Rossi R: An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 104(6): 947-953, 1988.
  4. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. American Journal of Medicine 97: 418-428, 1994.
  5. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. European Journal of Surgical Oncology 20: 613-621, 1994.
  6. 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): 958-964; discussion 964-966, 1998.
  7. 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. Journal of Nuclear Medicine 25(12): 1287-1293, 1984.
  8. 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): 1139-1147, 1992.

STAGE I FOLLICULAR THYROID CANCER

Surgery is the therapy of choice for all primary lesions. Surgical options include total thyroidectomy or lobectomy. The age of the patient and the size of the nodule influence the selection of the operative procedure. Survival results are similar; the difference between them lies in the rates of surgical complications and local recurrences.[1-5]

Treatment options:

Standard:

1. Total thyroidectomy: This procedure is advocated because of the high incidence of multicentric involvement of both lobes of the gland. However, it is associated with a higher incidence of hypoparathyroidism. This complication may be reduced when a small amount of tissue remains on the contralateral side. This approach facilitates follow-up thyroid scanning.

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. Follicular thyroid cancer commonly metastasizes to lung and bone; with a remnant lobe in place, use of I-131 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 not required.

Following the surgical procedure, patients should receive postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress TSH, since studies have shown a decreased incidence of recurrence.

I-131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I-131 results in a decreased recurrence rate in papillary and follicular carcinomas.[5] It should be given in addition to exogenous thyroid hormone.[6]

References:
  1. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1629-1652.
  2. Tollefsen HR, Shah JP, Huvos AG: Follicular carcinoma of the thyroid. American Journal of Surgery 126(4): 523-528, 1973.
  3. Edis AJ: Surgical treatment for thyroid cancer. Surgical Clinics of North America 57(3): 533-542, 1977.
  4. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. European Journal of Surgical Oncology 20: 613-621, 1994.
  5. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. American Journal of Medicine 97: 418-428, 1994.
  6. 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. Journal of Nuclear Medicine 25(12): 1287-1293, 1984.

STAGE II PAPILLARY 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 may be similar; the difference between them lies in the rates of surgical complications and local recurrences.[1-5]

Treatment options:

Standard:

1. 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. Patients under the age of 45 will have the longest follow-up period and the greatest opportunity for recurrence. 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 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 TSH, since studies have shown a decreased incidence of recurrence.

I-131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I-131 results in a decreased recurrence rate in papillary and follicular carcinomas.[5] It may be given in addition to exogenous thyroid hormone, but is not considered routine.[6]

2. Total thyroidectomy: This procedure is advocated because of the high incidence of multicentric involvement of both lobes of the gland and the question of de-differentiation of the 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.

References:
  1. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1629-1652.
  2. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: Is extent of surgical resection important? Surgery 104(6): 954-962, 1988.
  3. Cady B, Rossi R: An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 104(6): 947-953, 1988.
  4. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. European Journal of Surgical Oncology 20: 613-621, 1994.
  5. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. American Journal of Medicine 97: 418-428, 1994.
  6. 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. Journal of Nuclear Medicine 25(12): 1287-1293, 1984.

STAGE II FOLLICULAR THYROID CANCER

Surgery is the therapy of choice for all primary lesions. Surgical options include near total thyroidectomy and lobectomy. The age of the patient and the size of the nodule influence the selection of the operative procedure. Survival results are similar; the difference between them lies in the rates of surgical complications and local recurrences.[1-3]

Treatment options:

Standard:

1. Total thyroidectomy: This procedure is advocated because of the high incidence of multicentric involvement of both lobes of the gland. However, it is associated with a higher incidence of hypoparathyroidism. This complication is reduced when a small amount of tissue remains on the contralateral side. This approach facilitates follow-up thyroid scanning.

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. Follicular thyroid cancer commonly metastasizes to lung and bone; with a remnant lobe in place, use of I-131 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 node dissection is not required.

Following the surgical procedure, patients should receive postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress TSH, since studies have shown a decreased incidence of recurrence.

I-131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I-131 results in a decreased recurrence rate in papillary and follicular carcinomas. It should be given in addition to exogenous thyroid hormone.[4]

References:
  1. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1629-1652.
  2. Tollefsen HR, Shah JP, Huvos AG: Follicular carcinoma of the thyroid. American Journal of Surgery 126(4): 523-528, 1973.
  3. Edis AJ: Surgical treatment for thyroid cancer. Surgical Clinics of North America 57(3): 533-542, 1977.
  4. 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. Journal of Nuclear Medicine 25(12): 1287-1293, 1984.

STAGE III PAPILLARY THYROID CANCER

Treatment options:

Standard:

1. Total thyroidectomy plus removal of involved lymph nodes.

2. I-131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope.[1]

3. External-beam irradiation if I-131 uptake is minimal.

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. Journal of Nuclear Medicine 25(12): 1287-1293, 1984.

STAGE III FOLLICULAR THYROID CANCER

Treatment options:

Standard:

1. Total thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease.

2. I-131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope.[1]

3. External-beam irradiation if I-131 uptake is minimal.[2]

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. Journal of Nuclear Medicine 25(12): 1287-1293, 1984.
  2. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. American Journal of Surgery 136(4): 457-460, 1978.

STAGE IV PAPILLARY THYROID CANCER

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.

Treatment options:

Standard:

Distant metastases:
1. I-131: Metastases which demonstrate uptake of this isotope may be ablated by therapeutic doses of I-131.

2. External-beam irradiation for patients with localized lesions that are unresponsive to I-131.[1]

3. TSH suppression with T-4 is also effective in many of the non I-131 sensitive lesions.

4. Patients unresponsive to I-131 should also be considered candidates for investigative protocols testing new approaches to this disease.

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.[2-4] Refer to PDQ
or to CancerNet (http://cancernet.nci.nih.gov) for information on clinical
trials for patients with thyroid cancer.
References:
  1. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. American Journal of Surgery 136(4): 457-460, 1978.
  2. Gottlieb JA, Hill CS, Ibanez ML, et al.: Chemotherapy of thyroid cancer: an evaluation of experience with 37 patients. Cancer 30(3): 848-853, 1972.
  3. Marada T, Nishikawa Y, Suzuki T, et al.: Bleomycin treatment for cancer of the thyroid. American Journal of Surgery 122(1): 53-57, 1971.
  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): 2155-2160, 1985.

STAGE IV FOLLICULAR THYROID CANCER

Treatment of distant metastases is usually not curative but may produce significant palliation.

Treatment options:

Standard:

Distant metastases:
1. I-131: Metastases which demonstrate uptake of this isotope may be ablated by therapeutic doses of I-131.

2. External-beam irradiation for patients with localized lesions that are unresponsive to I-131.[1]

3. TSH suppression with T-4 is also effective in many of the non I-131 sensitive lesions.

4. Patients unresponsive to I-131 should also be considered candidates for investigative protocols testing new approaches to this disease.

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.[2-4] Refer to
PDQ or to CancerNet (http://cancernet.nci.nih.gov) for information on
clinical trials for patients with thyroid cancer.
References:
  1. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. American Journal of Surgery 136(4): 457-460, 1978.
  2. Gottlieb JA, Hill CS, Ibanez ML, et al.: Chemotherapy of thyroid cancer: an evaluation of experience with 37 patients. Cancer 30(3): 848-853, 1972.
  3. Marada T, Nishikawa Y, Suzuki T, et al.: Bleomycin treatment for cancer of the thyroid. American Journal of Surgery 122(1): 53-57, 1971.
  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): 2155-2160, 1985.

MEDULLARY THYROID CANCER

Medullary thyroid cancer (MTC) comprises 5% to 10% 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] Approximately 25% of reported cases of MTC are familial. Familial MTC syndromes include multiple endocrine neoplasia (MEN) 2A, which is the most common, MEN 2B, and familial non-MEN syndromes. 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. The overall survival of patients with MTC is 65% at 10 years. Poor prognostic factors include advanced age, advanced stage, prior neck surgery, and associated-MEN 2B.[3-5]

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, then 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.[6,7]

Patients with medullary thyroid cancer should be treated with a total thyroidectomy, unless there is evidence of distant metastasis. There should be careful sampling of the regional lymph nodes, unless others appear abnormal. If regional lymph nodes are involved, a (modified) radical neck dissection should be done.[8] When cancer is confined to the thyroid gland, the prognosis is excellent.

Radioactive iodine has no place in the treatment of patients with MTC. External radiation therapy has been used for palliation of locally recurrent tumors, without evidence that it provides any survival advantage.[9]

Palliative chemotherapy has been reported to produce occasional responses in patients with metastatic disease.[10-13] 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.

Refer to PDQ or to CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials for patients with thyroid cancer.

References:

  1. Soh EY, Clark OH: Surgical considerations and approach to thyroid cancer. Endocrinology and Metabolism Clinics of North America 25(1): 115-139, 1996.
  2. Giuffrida D, Gharib H: Current diagnosis and management of medullary thyroid carcinoma. Annals of Oncology 9(7): 695-701, 1998.
  3. Saad MF, Ordonez NG, Rashid RK, et al.: Medullary carcinoma of the thyroid: a study of the clinical features and prognostic factors in 161 patients. Medicine 63(6); 319-342, 1984.
  4. Giuffrida D, Gharib H: Current diagnosis and management of medullary thyroid carcinoma. Annals of Oncology 9(7): 695-701, 1998.
  5. Bergholm U, Bergstrom R, Ekbom A: Long term follow-up of patients with medullary carcinoma of the thryroid. Cancer 79(1): 132-138, 1997.
  6. Lips CJ, Landsvater RM, Hoppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. New England Journal of Medicine 331(13): 828-835, 1994.
  7. 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): 257-264, 1995.
  8. Bloch MA, Jackson CE, Tashjian AH: Management of occult medullary thyroid carcinoma. Archives of Surgery 113(4): 368-372, 1978.
  9. Brierley JD, Tsang RW: External radiation therapy in the treatment of thyroid malignancy. Endocrinology and Metabolism Clinics of North America 25(1): 141-157, 1996.
  10. 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): 2155-2160, 1985.
  11. De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. Journal of Endocrinological Investigation 14(6): 475-480, 1991.
  12. Wu LT, Averbuch SD, Ball DW, et al.: Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine. Cancer 73(2): 432-436, 1994.
  13. Orlandi F, Caraci P, Berruti A, et al.: Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Annals of Oncology 5(8): 763-765, 1994.

ANAPLASTIC THYROID CANCER

Treatment options:

Standard:

1. Surgery: Tracheostomy is frequently necessary. If the disease remains in the local area, which is indeed rare, total thyroidectomy is warranted to reduce symptoms caused by the tumor mass.[1,2]

2. Radiation therapy: External beam radiation therapy may be employed in those patients who are not surgical candidates or whose tumor cannot be surgically excised.

3. Chemotherapy: Anaplastic thyroid cancer is not responsive to I-131 therapy; treatment with single anticancer drugs has been reported to produce partial remissions in some patients. Approximately 30% of patients achieve partial remission with doxorubicin.[3] The combination of doxorubicin plus cisplatin appears to be more active than doxorubicin alone and has been reported to produce more complete responses.[4]

Under clinical evaluation:
Clinical trials evaluating new treatment approaches for this disease should
also be considered.[5] Refer to PDQ or to CancerNet
(http://cancernet.nci.nih.gov) for information on clinical trials for
patients with thyroid cancer.
References:
  1. Goldman JM, Goren EN, Cohen MH, et al.: Anaplastic thyroid carcinoma: long-term survival after radical surgery. Journal of Surgical Oncology 14(4): 389-394, 1980.
  2. Aldinger KA, Samaan NA, Ibanez ML, et al.: Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 41(6): 2267-2275, 1978.
  3. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1629-1652.
  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): 2155-2160, 1985.
  5. O'Mara R, Kartchner M, Salmon SE: High-risk thyroid cancer. Cancer Clinical Trials 4(1): 67-73, 1981.

RECURRENT THYROID CANCER

Patients treated for differentiated thyroid cancer should be followed carefully with physical examinations, thyroglobulin levels, and radiologic studies based on individual risk for recurrent disease.[1] Approximately 10% to 30% of patients felt to be disease-free after initial treatment will develop recurrence and/or metastases. Of patients who recur, approximately 80% recur with disease in the neck alone and 20% 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 following recurrence.[2] The prognosis for patients with clinically detectable recurrences is generally poor, regardless of cell type.[3] However, those patients who recur with local or regional tumor detected only by I-131 scan have a better prognosis.[4] The selection of further treatment depends on many factors, including cell type, uptake of I-131, prior treatment, site of recurrence, and individual patient considerations. Surgery with or without I-131 ablation can be useful in controlling local recurrences, regional node metastases, or occasionally metastases at other localized sites. Approximately half of the patients operated on for recurrent tumor can be rendered free of disease with a second operation.[3] Local and regional recurrences detected by I-131 scan and not clinically apparent can be treated with I-131 ablation and have an excellent prognosis.[5] Up to 25% of recurrences and metastases from well-differentiated thyroid cancer may not show I-131 uptake. For these patients, other imaging techniques shown to be of value include imaging with thallium-201, magnetic resonance imaging, and pentavalent dimercaptosuccinic acid.[6] When recurrent disease does not concentrate I-131, external-beam or intraoperative radiation therapy can be useful in controlling symptoms related to local tumor recurrences.[7] Systemic chemotherapy can be considered. Chemotherapy has been reported to produce occasional objective responses, usually of short duration.[4,8] Clinical trials evaluating new treatment approaches should also be considered. Refer to PDQ or to CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials for patients with recurrent thyroid cancer.

References:

  1. Ross DS: Long-term management of differentiated thyroid cancer. Endocrinology and Metabolism Clinics of North America 19(3): 719-739, 1990.
  2. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. American Journal of Medicine 97: 418-428, 1994.
  3. Goretzki PE, Simon D, Frilling A, et al.: Surgical reintervention for differentiated thyroid cancer. British Journal of Surgery 80(8): 1009-1012, 1993.
  4. De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. Journal of Endocrinological Investigation 14(6): 475-480, 1991.
  5. Coburn M, Teates D, Wanebo HJ: Recurrent thyroid cancer: role of surgery versus radioactive iodine (I131). Annals of Surgery 219(6): 587-595, 1994.
  6. Mallin WH, Elgazzar AH, Maxon HR: Imaging modalities in the follow-up of non-Iodine avid thyroid carcinoma. American Journal of Otolaryngology 15(6): 417-422, 1994.
  7. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. American Journal of Surgery 150(4): 485-487, 1985.
  8. 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): 2155-2160, 1985.

Date Last Modified: 06/1999

 
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