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Management of Thyroid Carcinoma: Key Considerations
Thyroid cancer occurs as frequently as many other more publicized cancers.
Reviewed by Gerard M. Doherty, MD; and Mira Milas, MD, FACS; By Conni Bergmann Koury, Editor-in-Chief
According to the American Association of Clinical Endocrinologists (AACE), the American College of Endocrinology (ACE), and the American Association of Endocrine Surgeons (AAES), thyroid cancer is the "forgotten cancer."1 It occurs as frequently as other more publicized cancers—approximately 37,000 new cases were diagnosed in the United States in 2008, according to the American Cancer Society.2 Many thyroid cancers are curable with an excellent prognosis.1,3 About 1,590 poeple died from thyroid cancer in 2008, but 190,000 patients are survivors.2,4
Gerard M. Doherty, MD, the NW Thompson Professor of Surgery and Head, Section of General Surgery at the University of Michigan, told Review of Endocrinology in an e-mail interview that thyroid cancer is often overlooked and underestimated because it causes few deaths. "This is good news, as our treatments are very effective," he said. "Thorough initial surgery can decrease the number of necessary ongoing tests and treatments, so it is important to ensure optimal treatment from the outset."
Thyroid cancer has a "kinder public face" compared with other cancers, according to Mira Milas, MD, FACS, Staff Surgeon and Director of the Thyroid Center in the Endocrinology and Metabolism Institute at the Cleveland Clinic. "It is nevertheless important to advocate for progress in thyroid cancer care, as subsets of patients with much more aggressive disease do exist," she said in an e-mail to Review of Endocrinology.
HIGH-QUALITY, COST-EFFECTIVE CARE
The AACE/AAES guidelines emphasize high-quality, cost-effective care with the avoidance of overly aggressive treatment for those who have excellent prognoses and with adequate therapy for those at high risk of recurrence and death.
General endocrinologists are key in the treatment of patients with thyroid cancer because patients require lifelong surveillance and ongoing monitoring and follow-up. Management of thyroid cancer can be, however, a controversial topic. "Because thyroid cancer causes few deaths, any morbidity of treatment affects patients for a long time," Dr. Doherty said. "Operations that are safe and effective when performed by experienced surgeons, can cause long-term problems when attempted by those who perform thyroidectomy only occasionally."
Dr. Milas added that because thyroid cancer behaves favorably in general, survival and recurrence endpoints require years, if not decades, to manifest, making it difficult to design studies that give timely answers to "best" approaches. "In the surgical community, the issue of total thyroidectomy is currently less controversial than that of prophylactic central neck dissection," Dr. Milas said.
CANCER TYPES
Thyroid nodules are common, however malignant lesions are relatively rare (<1% of all human malignant tumors). Despite this infrequency, thyroid cancer is the most common endocrine malignant lesion.
Follicular thyroid cells, which make thyroglobulin and produce and store thyroxine and triiodothyronine, and C cells or parafollicular cells, which produce calcitonin, are the two main types of cells in the thyroid.3 Each gives rise to different types of cancer.
Papillary and follicular cancers that develop from the follicular cells account for the majority of thyroid cancers. Generally, these can be surgically removed with an excellent prognosis. Medullary cancer that arises from the C cells is generally more aggressive and therefore more difficult to treat.
There are five types of thyroid cancer:
- papillary cancer
- follicular cancer
- medullary cancer
- anaplastic cancer
- thyroid lymphoma
SURGICAL MANAGEMENT
Experts agree that fine-needle aspiration (FNA) biopsy is crucial to the diagnosis of thyroid cancer.1 The step-by-step management beyond that, however, is somewhat controversial. Issues include the extent of primary surgical resection; the need for and extent of regional lymph node dissection; the role of postoperative radioiodine remnant ablation (RRA) in follicular cell-derived cancers (FCDC), also referred to as differentiated thyroid cancers; and the degree to which suppression of thyroid-stimulating hormone (TSH) is needed in the long-term management of FCDC.1
Surgical treatment is the preferred management initially in almost all patients with thyroid cancer, and most surgeons will perform a near-total thyroidectomy. Many FCDC patients are treated with RRA and few require postoperative external irradiation or chemotherapy. Patients are at risk of recurrence, therefore, long-term surveillance is necessary. A team approach to these patients is necessary for optimal care.
According to Dr. Doherty, surgery is the base treatment for nearly all thyroid cancer patients because (1) it results in a cure in most patients, (2) it allows radioiodine treatment to follow, and (3) it protects the mechanisms that control breathing, speaking, and swallowing in those patients who cannot be cured.
Surgery can technically be accomplished in virtually all thyroid cancer patients, Dr. Milas added, providing definitive removal of the primary cancer. "There is no known medical therapy that can as effectively clear gross or measurable foci of thyroid cancer."
Surgery with intent to cure is not preferred for those rare patients with, typically, poorly differentiated or anaplastic cancers whose imaging studies reveal advanced involvement of critical normal structures, making the cancer unresectable, according to Dr. Milas. "Palliative surgery, such as tracheostomy for airway preservation, may be the only option," she said. Also, patients with small cancers who are medically unfit for anesthesia and surgery require medical management.
According to the American Thyroid Association statement,5 there are six goals of initial therapy of differentiated thyroid cancer: (1) to remove the primary tumor, disease that has extended beyond the thyroid capsule, and involved cervical lymph nodes; (2) to minimize treatment- and disease-related morbidity; (3) to permit accurate staging of the disease; (4) to facilitate postoperative treatment with RRA where appropriate; (5) to permit accurate long-term surveillance for disease recurrence; and (6) to minimize the risk of disease recurrence and metastatic spread.
Papillary thyroid carcinoma (PTC). According to AACE/AAES guidelines, ipsilateral thyroid lobectomy is generally accepted as the minimal surgical procedure for a unilateral, possibly malignant thyroid nodule. Total or near-total thyroidectomy is the preferred course of action for high-risk PTC patients and recently is being advocated for those with known, FNA-proven PTC cancers >1 cm. There are differing opinions regarding the extent of resection for patients with low-risk PTC and cancers <1 cm. The guidelines state that the postoperative use of 131I (radioiodine) is facilitated by total or near-total thyroidectomy. After total thyroidectomy, thyroglobulin is a more sensitive indicator of residual disease.
Follicular thyroid carcinoma (FTC). This type of cancer cannot be diagnosed before surgery using FNA. In patients with FTC, a typical result from FNA may be described generally as a follicular neoplasm. These neoplasms are benign about 80% of the time; however, the larger ones are more likely to be malignant—especially in men aged >50 years. Thus, a commonly used strategy is to perform a lobectomy first to comfirm whether there is in fact thyroid cancer. The 80% of patients who have a benign pathology report may only require the lobectomy. Those patients who are comfirmed to have FTC are advised to have a total thyroidectomy. This may require a second surgery to remove the remaining thyroid lobe, and some clinicians may choose to use radioactive iodine (RAI) postoperatively. Much research has been invested into trying to determine which patients with follicular neoplasms on FNA do in fact have malignancy, and a number of promising molecular markers are in clinical use.
Medullary thyroid carcinoma (MTC). About 6% to 8% of thyroid cancers are MTC, with 75% being sporadic and 25% hereditary, according to AACE/AAES. Surgery for sporadic MTC should include total thyroidectomy, central compartment lymph node dissection, and possibly ipsilateral modified radical neck dissection.6
Calcitonin levels should be measured 8 to 12 weeks following surgery to assess the presence of residual disease and then be monitored throughout the patient's lifetime.
Hereditary MTC can be part of an inherited syndrome known as multiple endocrine neoplasia, type II (MEN2), or it can run in families in an hereditary fashion but not be part of MEN2. The hereditary MTC cancers appear much earlier in life than other thyroid cancers, and individuals with MEN2 usually have tumors in the adrenal or parathyroid glands as well as the thyroid. There are two subtypes of MEN2—MEN2A and MEN2B. Individuals with MEN 2A often develop pheochromocytomas (adrenal tumors causing hypertension) and tumors of the parathyroid glands. Those patients with MEN2B also have adrenal gland tumors and uniquely have neuromas, but they do not have parathyroid gland problems.3
Genetic counseling and evaluation are advised for patients diagnosed with MTC. Surgical treatment of the thyroid is then recommended for MTC family members diagnosed with the corresponding genetic mutations. For such patients, a prophylactic total thyroidectomy and central compartment lymph node dissection are indicated even if the thyroid gland does not yet have detectable abnormalities.7
Anaplastic thyroid carcinoma. This is a highly aggressive, uncommon tumor and treatment is controversial. Although external beam radiotherapy can help control the disease, the neoplasm is considered radioresistant compared with other solid neoplasms. Chemotherapy may prolong survival, but is not successful in changing the fatal outcome. Therefore, local tumor control may be the most practical management strategy, if surgically possible.
Thyroid lymphoma. Thyroid lymphoma can develop in thyroid glands affected with thyroiditis, such as Hashmito's thyroiditis. Surgery, if possible, and lymphoma-based chemotherapy treatments are involved. These rare cancers are best referred to thyroid specialists if a concern for lymphoma exists.
ADJUVANT THERAPY
Thyroid hormone. The use of supraphysiologic doses of thyroid hormone to suppress serum TSH in FCDC has been a part of treatment for more than four decades.8,9 Levothyroxine has been shown to decrease cancer-related death rates among patients with PTC, and tumor recurrence rates in PTC and FTC are reduced with suppressive therapy.9
RRA. RAI is often used in FCDC patients to ablate residual thyroid tissue after surgery (RRA).10 At the same time, this RAI treatment also destroys any residual microscopic thyroid cancer following initial surgery. Larger doses of 131I may be administered to destroy more persistent neck disease or distant metastatic lesions, according to the AACE/AAES guidelines.
PRESISTENT OR RECURRENT DISEASE
Secondary surgical intervention. Surgical excision is the usual therapy of choice for locally recurrent FCDC. Bulky lesions should be considered for surgery if 131I is not effective, according to the AACE/AAES.
Reoperations for thyroid cancer have substantially higher risks and a much higher degree of complexity than initial operations, Dr. Doherty said. "The risk of complications from reoperation in areas where disease has been removed previously is about six times greater than the initial attempt. This is one of the reasons that a safe, thorough initial operation is so important," he added.
The value of identifying cervical nodal metastases initially—most easily done with ultrasound—so that a patient can undergo simultaneous thyroidectomy and neck dissection and potentially avoid reoperation, cannot be underestimated, Dr. Milas said.
Radioactive iodine. Radioiodine (131I) is typically administered to patients with FCDC when metastatic disease is discovered during follow-up.11,12
External irradiation. Although external irradiation is rarely used as adjunctive therapy in the initial management of FCDC patients,13,14 it may be beneficial in select patients, such as those with poorly differentiated tumors that do not concentrate RAI or those with more gross residual disease that cannot be surgically removed.
Chemotherapy. "More so now than ever before, there are prominsing chemotherapy options to treat patients with recurrent thyroid cancer when surgery and RAI are ineffective," Dr. Milas said.
CONCLUSION
Thyroid cancer recurrence rates depend on a number of factors, including the histological subtype of the cancer, the presence of lymph node metastases or extrathyroidal extension at original surgery, and the patient's age and gender, Dr. Milas said.
"For differentiated thyroid cancer, rates range from 10-year recurrence rates of 7% to overall lifetime recurrence rates of 30%," she said. "Medullary thyroid cancer recurrence is more frequent. A significant majority of all recurrences will be in the form of cervical nodal metastases, rather than distant metastases."
The pattern of recurrence emphasizes the need for ongoing surveillance. "Even with recurrence, patients can often be cured, or treated carefully to live for long periods of time in spite of incurable disease," Dr. Doherty said.
Experts note that this field is highly complex and there are many differing opinions. It is important that endocrinologists are aware of their role to coordinate comprehensive care in thyroid cancer patients.
Gerard M. Doherty, MD, is the NW Thompson Professor of Surgery and Head of the Section of General Surgery at the University of Michigan. He may be reached at gerardd@med.umich.edu; phone: 734-615-4741; or fax: 734-936-5830. Mira Milas, MD, FACS, is Staff Surgeon and Director of the Thyroid Center, Cleveland Clinic Lerner College of Medicine. She may be reached at milasm@ccf.org; phone: 216-444-4985; or fax: 216-636-0662.
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