Approach Considerations
Surgery is the definitive management of papillary thyroid cancer.
Indirect or fiberoptic laryngoscopy is performed as part of preoperative planning to evaluate airway and vocal cord mobility and to document any unrelated abnormalities.
Approximately 4-6 weeks after surgical thyroid removal, patients may have radioiodine therapy to detect and destroy any metastasis and residual tissue in the thyroid.
External beam radiotherapy has been used as adjuvant therapy in patients with papillary thyroid cancer who were older than 45 years and had locally invasive disease. Some improvements in 10-year survival rates have been reported with this approach.
Patients require lifelong thyroid hormone replacement therapy, especially after total thyroidectomy. Treatment consists of levothyroxine in a dosage of 2.5-3.5 mcg/kg/d.
For summarized information on treatment, see Thyroid Cancer Treatment Protocols.
Surgical Care
Surgery is the definitive management of thyroid cancer. Various types of operations may be performed, ranging from lobectomy with isthmectomy to total thyroidectomy.
Lobectomy with isthmectomy is the minimal operation for a potentially malignant thyroid nodule. It is an option for patients younger than 40 years who have papillary thyroid carcinoma nodules that are smaller than 1 cm, well-defined, minimally invasive, and isolated. However, an important consideration for this approach is that approximately 10% of patients who have had only a lobectomy develop a recurrence in the contralateral lobe, and residual tissue has the potential to dedifferentiate to anaplastic cancer.
Subtotal thyroidectomy is a near-total thyroidectomy. The argument for this form of surgical intervention is that total thyroidectomy does not improve long-term prognosis, and subtotal thyroidectomy has a lower incidence of complications (eg, hypoparathyroidism, superior and/or recurrent laryngeal nerve injury) than total thyroidectomy.
Total thyroidectomy
Total thyroidectomy (removal of all thyroid tissue but preservation of the parathyroid glands) is commonly performed for patients with papillary carcinoma who are older than 40 years and in any patient with bilateral disease. In addition, total thyroidectomy is used in most patients with a thyroid nodule and a history of irradiation.
National Comprehensive Cancer Network guidelines recommend total thyroidectomy for patients who meet any of the following criteria [8] :
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Radiation history
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Known distant metastases
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Bilateral nodularity
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Extrathyroidal extension
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Tumor >4 cm in diameter
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Cervical lymph node metastases
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Poorly differentiated tumor
Total thyroidectomy is considered by many to be the surgical treatment of choice for papillary tumors of the thyroid, for a number of reasons. Papillary foci involving both lobes are found in some 60-85% of patients. About 5-10% of patients who have had a lobectomy develop recurrences in the remaining lobe. Also, at 20 years after initial surgery, patients who had undergone total thyroidectomy had a recurrence rate of 8%, whereas those who had received only lobectomy had a recurrence rate of 22%. Survival rates were, however, comparable.
Total thyroidectomy also facilitates earlier detection and treatment of recurrent or metastatic carcinoma. This surgical option is mandatory in patients with papillary carcinoma discovered on postoperative histology (ie, if a very well-differentiated tumor is discovered) after a lobectomy, with or without isthmectomy.
When the primary tumor spreads outside the thyroid and involves adjacent vital organs (eg, larynx, trachea, esophagus), these organs are preserved at the first surgical approach. However, the surrounding soft tissues, including the muscles and involved areas of the trachea and/or esophagus, may be sacrificed if they are directly involved with the differentiated thyroid carcinoma and local resection is feasible.
Surgical techniques include video-assisted and robotic-assisted thyroidectomy. [49, 50] Video-assisted thyroidectomy is rarely used to treat thyroid cancer. A study by Lee et al found that the application of robotic technology to endoscopic thyroidectomy may overcome the limitations of conventional surgery, in a patient population where neck incision is considered culturally averse. However, additional complications such as brachial plexus injury may occur with this technique. [51]
Central neck dissection
The routine addition of central neck dissection to total thyroidectomy has been debated over the years. Advocates cite a lower risk of later reoperation, since reoperations for recurrence can lead to higher rates of recurrent nerve injury. Critics cite the fact the upfront recurrent nerve injury rate may be higher and that no survival benefit has been demonstrated over total thyroidectomy alone. In a retrospective cohort study of 812 patients with papillary thyroid carcinoma, including 102 who underwent total thyroidectomy with elective central neck dissection and 478 who underwent total thyroidectomy alone, elective central neck dissection increased the risk for complications, but did not decrease local recurrence rates. [52]
A study by Roh et al found that subclinical metastases are highly prevalent in the ipsilateral central neck of patients with papillary thyroid carcinoma. The study also revealed that although contralateral central metastases are uncommon, they are associated with ipsilateral central metastases. The authors conclude that these findings may suggest the necessity and extent of prophylactic unilateral or bilateral central lymph node dissection. [53]
A study by Popadich et al found that the addition of routine central lymph node dissection in patients with cN0 papillary thyroid carcinoma reduced the need for reoperation in the central compartment and was associated with lower postoperative thyroglobulin levels. [54]
Complications
Surgical treatment of thyroid cancer may cause complications, partly because of the variable anatomy of the neck. These possible complications include the following:
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Dysphagia due to damage of the upper laryngeal nerve
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Vocal cord paralysis due to damage of the recurrent laryngeal nerve
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Hypoparathyroidism due to parathyroid gland ablation
Radioiodine Therapy
Approximately 4-6 weeks after surgical thyroid removal, patients may have radioiodine therapy to detect and destroy any metastasis and residual tissue in the thyroid. The decision for radioactive iodine depends on the size of the tumors removed, the prognostic features (eg, lymphovascular invasion) and the individual endocrinologist’s level of aggressiveness and interpretation of the literature. Patients with low-risk differentiated papillary thyroid cancer have shown excellent responses to total thyroidectomy without radioiodine remnant ablation. [55]
After thyroidectomy, patients are given thyroid replacement therapy for approximately 4-6 weeks. Thyroid replacement is then discontinued, to induce a hypothyroid state and promote high serum thyroid-stimulating hormone (TSH) levels.
A diagnostic dose of radioiodine (131I or 123I) is then given, and a whole-body scintiscan is performed to detect any tissue taking up radioiodine. If any normal thyroid remnant or metastatic disease is detected, a therapeutic dose of 131I is administered to ablate the tissue. The patient is then placed back on thyroid hormone replacement (levothyroxine) therapy.
Therapy is administered until radioiodine uptake is completely absent. Radioiodine treatment may be used again 6-12 months after initial treatment of metastatic disease, for cases in which disease recurs or has not fully responded.
Some patients have elevated stimulated thyroglobulin concentrations after reoperation for recurrent or persistent papillary thyroid cancer. Yim and colleagues found that in such patients, adjuvant radioiodine therapy resulted in no significant differences compared with no additional radioiodine therapy. [56]
Patients receiving radioiodine therapy need to follow radiation precautions, to maintain the safety of themselves, their familes, and the public. The American Thyroid Association Taskforce on Radioiodine Safety released recommendations to help guide physicians and patients in safe practices after treatment, including reminders in the form of a checklist. [57]
Complications
Potential adverse effects of radioiodine administration include the following:
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Radiation thyroiditis and transient thyrotoxicosis in patients with simple lobectomy
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Sialoadenitis, because radioiodine is taken up by the salivary glands
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Nausea, anorexia, and headache (uncommon)
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Pulmonary fibrosis in patients with large lung metastases
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Brain edema in patients with brain metastases (may be prevented by glucocorticoid therapy)
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Permanent sterility and transient oligospermia or menstrual irregularities
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Teratogenesis and spontaneous abortions
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A small increase in the risk for leukemias (in particular, acute myeloid leukemia [58] ) or breast and bladder carcinomas
Because radioiodine treatment may cause either teratogenesis or spontaneous abortions, patients should delay pregnancy for at least 1 year after radioiodine treatment.
Treatment of Advanced Disease
A study by Heilo et al determined that ultrasonography-guided percutaneous ethanol injections were an excellent alternative to surgery in patients with a limited number of neck metastases from papillary thyroid carcinoma. The authors suggest that this strategy could replace “berry picking” surgery. [59]
In patients with stage T4 disease, external beam radiation therapy (EBRT) may be performed to control local tumor growth in areas such as the neck, lungs, mediastinum, bone, and central nervous system.
Chemotherapy with cisplatin or doxorubicin has limited efficacy, producing occasional objective responses (generally for short durations), and high toxicity. Chemotherapy may be considered in symptomatic patients with recurrent or advancing disease, and it may improve the quality of life in patients with bone metastases. However, a standard protocol for chemotherapeutic management has not been developed for these patients.
Novel agents are under active investigation as options for systemic therapy. [60] Agents that have been studied in patients with metastatic thyroid carcinoma include multitargeted kinase inhibitors (eg, levatinib, sorafenib, sunitinib, axitinib, vandetanib, pazopanib, cabozantinib) and BRAF V600E mutation inhibitors (eg, vemurafinib, dabarafenib). [61] Preliminary data suggest that anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib may be useful in PTC with fusion of the striatin (STRN) and the ALK genes. [62]
A discussion of recently available targeted therapies for use in advanced differentiated thyroid cancer no longer responsive to radioablation may be found in the Chemotherapy section of Follicular Thyroid Carcinoma.
Consultations
Consult an otolaryngologist, especially in thyroid patients who have voice disturbances. Systematic psychotherapeutic intervention may be very helpful.
Long-term Monitoring
Repeat the radioiodine scintiscan 6-12 months after ablation and every 2 years thereafter. Before the scan, levothyroxine must be withdrawn for approximately 4-6 weeks to maximize thyrotropin stimulation of the any remaining thyroid tissue.
At 6 and 12 months after the cancer treatment (medical or surgical),patients with a history of papillary thyroid carcinoma require follow-up monitoring that includes the following:
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Complete physical examination
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Thyroid-stimulating hormone (TSH) and thyroglobulin measurement
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Antithyroglobulin antibodies titer
Continue to evaluate thyroglobulin serum levels every 6-12 months for at least 5 years. Consider a level greater than 20 ng/mL, after TSH suppression, to be abnormal. A rise in the thyroglobulin level is consistent with recurrence of thyroid cancer. A study by Brassard et al found that thyroglobulin measurements allow prediction of long-term recurrence with excellent specificity. TSH stimulation may be avoided when thyroglobulin levels measured 3 months after ablation are less than 0.27 ng/mL during levothyroxine treatment. [63]
Perform thyroid hormone suppression tests in all patients who have undergone total thyroidectomy and in all patients who have had radioactive ablation of any remaining thyroid tissue. Individualize the degree of suppression to avoid complications, such as subclinical hyperthyroidism.
In patients who were treated with radioactive iodine ablation and who have a negative thyroid ultrasound, a stimulated thyroglobulin level < 2 ng/mL with negative antithyroglobulin antibodies, and negative radioactive iodine imaging (if performed), the National Comprehensive Cancer Network advises that follow-up may consist of annual measurement of unstimulated thyroglobulin levels and periodic neck ultrasound. TSH-stimulated testing or other imaging, as clinically appropriate, may be considered if there is any clinical suggestion of recurrent disease. [8]
A meta-analysis demonstrated that an undetectable serum thyroglobulin finding during thyroid hormone suppression of TSH is often misleading. Patients with endogenous subclinical hyperthyroidism have an increased risk of cardiovascular disease and dysrhythmia. [64] Accordingly, the authors propose a new surveillance guideline for patients who have undergone total or near-total thyroidectomy and radioactive iodine ablation and have no clinical evidence of residual tumor with a serum thyroglobulin level less than 1 mcg/L during thyroid hormone suppression of TSH.
Subclinical hypothyroidism may also occur. However, the clinical significance of subclinical hypothyroidism, and the benefits of treating it, remain uncertain. [65, 66]
Guidelines from the American Association of Clinical Endocrinologists (AACE) and the American Association of Endocrine Surgeons include recommendations for follow-up in patients with thyroid carcinoma. [7]
Patients require lifelong thyroid hormone replacement therapy, especially after total thyroidectomy. Treatment consists of levothyroxine in a dosage of 2.5-3.5 mcg/kg/d. A patient who has had a thyroidectomy without parathyroid preservation requires vitamin D and calcium supplementation for life.
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Standard open thyroidectomy.
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Algorithm for the workup of a solitary thyroid nodule. FNAB = fine needle aspiration biopsy.
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Planar and color Doppler image showing a cystic papillary thyroid carcinoma.
Tables
| Race | Females | Males |
|---|---|---|
| White | 30.8 | 14.3 |
| Black | 18.5 | 5.6 |
| Asian/Pacific Islander | 37.2 | 10.5 |
| American Indian/Alaska Native | 41.7* | —* |
| Hispanic | 32.8 | 10.3 |
