Follicular Thyroid Carcinoma Treatment & Management

Updated: Jun 18, 2020
  • Author: Luigi Santacroce, MD; Chief Editor: Neetu Radhakrishnan, MD  more...
  • Print
Treatment

Approach Considerations

The initial treatment for cancer of the thyroid is surgical. The exact nature of the surgical procedure to be performed depends for the most part on the extent of the local disease. A consensus approach might be to perform a total thyroidectomy if the primary tumor is larger than 1 cm in diameter or if there is extrathyroidal involvement or distant metastases. Clinically evident lymphadenopathy should be removed with a neck dissection. If the primary tumor is less than 1 cm in diameter, a unilateral lobectomy might be considered.

Current National Comprehensive Cancer Network (NCCN) guidelines recommend lobectomy plus isthmusectomy as the initial surgery for patients with follicular neoplasms, with prompt completion of thyroidectomy if invasive follicular thyroid carcinoma (FTC) is found on the final histologic section. Therapeutic neck dissection of involved compartments is recommended for clinically apparent/biopsy-proven disease. [1]

The NCCN recommends total thyroidectomy as the initial procedure only if invasive cancer or metastatic disease is apparent at the time or surgery, or if the patient wishes to avoid a second, completion thyroidectomy should the pathologic review reveal cancer. [1]

About 4-6 weeks after surgical thyroid removal, patients must have radioiodine to detect and destroy any metastasis and any residual tissue in the thyroid. Administer therapy until no further radioiodine uptake is noted.

Patients take thyroid replacement therapy (ie, levothyroxine [L-T4]) for life. This entails taking 2.5-3.5 mcg/kg of L-T4 every day. The thyroxine is given in the dose necessary to inhibit thyrotropin to a value of 0.1-0.5 mU/L. This treatment plan is generally successful. However, a 10-year recurrence rate of 20-30% may be seen in older patients, in patients with primary tumors greater than 4 cm in diameter, and in patients where tumor has spread beyond the thyroid boundaries and where lymph node involvement is widespread. Once metastatic thyroid cancer becomes resistant to radioiodine, the 10-year survival is less than 15%.

A number of indications for external beam radiation therapy (EBRT) apply to the management of FTC. If all gross disease cannot be resected, or if residual disease is not avid for radioactive iodine, EBRT is often employed for locally advanced disease.

Similarly, radiation therapy is indicated for unresectable disease extending into adjacent structures, such as the trachea, esophagus, great vessels, mediastinum, and/or connective tissue. In this situation, radiation therapy doses of 6000-6500 cGy are typically used. Following radiation therapy for unresectable disease, the patient should undergo radioactive iodine (I-131) scanning. If uptake is detected, a dose of I-131 should be administered.

EBRT increases the local-regional control of the residual disease for patients with locally advanced differentiated thyroid carcinoma. [24] EBRT also may be used after resection of recurrent FTC that is no longer avid for radioactive iodine.

In the postoperative setting, radiation therapy doses of 5000-6000 cGy are commonly delivered to the tumor bed to reduce the risk of local-regional recurrence.

Careful treatment planning (typically with multiple radiation therapy fields) should be employed to minimize the risks of radiation therapy complications.

Finally, a palliative course of radiation therapy is useful to relieve pain from bone metastases.

Chemotherapy with cisplatin or doxorubicin has limited efficacy, producing occasional objective responses (generally for short durations). Because of the high toxicity of cisplatin and doxorubicin, chemotherapy may be considered in symptomatic patients with recurrent or progressive disease. It could improve quality of life in patients with bone metastases. No standard protocol exists for chemotherapy of metastatic FTC.

FTC is a highly vascular lesion. In patients with bone metastases who experience severe pain that does not respond to palliative radiation, arterial embolization of the tumor might be considered.

The possible involvement of angiogenesis in the progression of metastatic thyroid carcinoma has suggested a role for the multikinase inhibitor sunitinib, which may inhibit angiogenesis. A phase II trial in 23 patients with advanced differentiated thyroid cancer who had received at least one course of radioactive iodine treatment demonstrated that sunitinib exhibits significant anti-tumor activity. Of the 23 patients, six (26%) achieved a partial response and 13 (57%) had stable disease. [25]

See Thyroid Cancer Treatment Protocols for summarized information.

Next:

Surgical Care

Surgery is the definitive management of thyroid cancer, and various types of operations may be performed. 

In a study by Asari et al of 207 patients with FTC, the 127 patients with minimally invasive growth had no lymph node metastases. According to the authors, total thyroidectomy is recommended for all patients with FTC, but patients with widely invasive FTC need more aggressive surgery because of a higher tendency toward lymph node metastases. Patients with minimally invasive disease have an excellent prognosis with a limited need for nodal surgery, according to this study. [26]

In a study by Spinelli et al of pediatric patients with FTC (age 18 years and younger), total thyroidectomy was performed in 9 of the 30 patients; 21 initially underwent hemithyroidectomy, but 11 of those subsequently required completion of thyroidectomy. [27]  The authors conclude that a conservative approach to surgery seems valid for pediatric patients diagnosed with minimally invasive FTC; they recommend completion of thyroidectomy for patients with wide vascular invasion and/or a tumor > 4 cm, especially with a high postoperative thyroglobulin level, and advise that total thyroidectomy followed by radioiodine therapy is generally indicated for patients with one or more of the following:

  • Multifocal neoplasia
  • Tumor size ≥4 cm
  • Extrathyroid extension
  • Lymph node metastasis
  • Distant metastasis

Lobectomy with isthmectomy

This represents the minimal operation for a potentially malignant thyroid nodule.

A study of 889 thyroid cancer patients who underwent either total thyroidectomy or thyroid lobectomy showed similarly high rates of survival among both groups. [28] Patients younger than 40 years who have FTC nodules that are less than 1 cm in size, well defined, minimally invasive, and isolated may be treated with hemithyroidectomy and isthmectomy.

Subtotal thyroidectomy (near-total thyroidectomy)

Subtotal thyroidectomy is preferable if it is feasible, since it carries a lower incidence of complications (eg, hypoparathyroidism, superior and/or recurrent laryngeal nerve injury).

Moreover, total thyroidectomy does not improve the long-term prognosis.

Total thyroidectomy (removal of all thyroid tissue, with preservation of the contralateral parathyroid glands)

Approximately 10% of patients who have had total thyroidectomy demonstrate cancer in the contralateral lobe. Therefore, residual thyroid tissue has the potential to dedifferentiate to anaplastic cancer.

Perform total thyroidectomy in patients with FTC who are older than 40 years and in any patient with bilateral disease; furthermore, recommend total thyroidectomy to anyone with a thyroid nodule and a history of irradiation.

Some studies show lower recurrence rates and increased survival rates in patients who have undergone total thyroidectomy. This surgical procedure also facilitates earlier detection and treatment of recurrent or metastatic carcinoma. This surgical option is mandatory in patients with FTC ascertained by postoperative histologic studies (ie, if a very well-differentiated tumor is discovered) after a one-side lobectomy, with or without isthmectomy.

When the primary tumor has spread outside the thyroid and involves adjacent vital organs, such as the larynx, trachea, or esophagus, preserve these organs at the first surgical approach. However, the surrounding soft tissues, including muscles and involved areas of the trachea and/or esophagus, may be sacrificed whenever they are involved directly in the differentiated thyroid carcinoma and their local resection is easily feasible. Surgical resection of one or more brain metastases may prolong survival from 4 to 22 months.

Minimally invasive techniques

A number of minimally invasive approaches have been develpoed for the treatment of thyroid carcinoma, including minimally invasive video-assisted thyroidectomy (MIVAT), transaxillary endoscopic thyroidectomy, and robotic thyroidectomy. [29]

Robotic-assisted thyroidectomy

A study by Lee et al found that the application of robot technology to endoscopic thyroidectomy may overcome the limitations of conventional surgery. [30] A systematic review and meta-analysis by Jackson et al of robotic thyroidectomy via a gasless, axillary approach found that operative time was longer with robotic than conventional thyroidectomy, but with a trend to be shorter than with endoscopic approaches. Risks of robotic surgery were similar to those of open and endoscopic approaches. Compared with patients undergoing conventional thyroidectomy, patients who underwent robotic surgery reported greater cosmetic satisfaction. [31]

Previous
Next:

Consultations

Schedule elderly patients for cardiologic assessment because of the high risk of subclinical hypothyroidism episodes.

Consult an otolaryngologist, especially in patients with thyroid disease who have voice disturbances.

Previous
Next:

Complications

If it is neglected, FTC may produce symptoms due to the compression and/or infiltration of the surrounding tissues, and it may metastasize to lung and bone.

Surgical treatment of FTC may cause complications, partially because of the variable anatomy of the neck. Complication rates, especially with total thyroidectomy, are lower in the hands of experienced surgeons. [32]  Possible complications include the following:

Radioiodine administration may have the following consequences:

  • Radiation thyroiditis and transient thyrotoxicosis in patients who have undergone simple lobectomy

  • Sialoadenitis, because radioiodine is taken up by the salivary glands

  • Nausea, anorexia, and headache (uncommon)

  • Pulmonary fibrosis in patients with large lung metastases

  • Brain edema in patients with brain metastases (this may be prevented by glucocorticoid treatment)

  • Permanent sterility and transient oligospermia or menstrual irregularities

  • Teratogenesis and spontaneous abortions

  • A slight increase in the risk of leukemias or breast and bladder carcinomas.

In a study of 438 patients with thyroid cancer, similar outcomes were achieved with low-dose radioiodine plus thyrotropin alfa treatment and high-dose radioiodine treatment, and low-dose treatment was associated with a lower rate of adverse events. [34]

The most frequent sites of metastasis are lung and bone, followed by the brain and the liver; metastasis to other sites occurs less frequently. Metastatic potential seems to be a function of primary tumor size; however, metastases without thyroid pathology identified on physical examination may be found in patients with microscopic FTC.

Previous
Next:

Long-Term Monitoring

Perform postoperative scintiscan of the neck after 4-6 weeks without thyroid hormone replacement. At this time, a scan of the neck demonstrates whether thyroid tissue is still present. If thyroid tissue is present, a dose of radioactive iodine is administered to destroy residual tissue. The patient is then placed on lifelong thyroid replacement with L-T4. Repeat the scintiscan 6-12 months after ablation and, thereafter, every 2 years. Prior to the scan, L-T4 must be withdrawn for approximately 4-6 weeks to maximize thyrotropin stimulation of any remaining thyroid tissue.

Radioactive iodine may ablate the metastatic tissue in the lungs and bone. In fact, metastases of FTC appear to be more amenable to radioiodine therapy than metastases of papillary carcinoma.

For a single CNS metastasis, consider neurosurgical resection and radioiodine treatment, perhaps combined with recombinant human thyroid-stimulating hormon (rhTSH) and steroids, and/or radiation therapy.

Evaluate thyroglobulin serum levels every 6-12 months for at least 5 years. Consider a level higher than 20 ng/mL, after TSH suppression, to be abnormal. A recurrence of thyroid cancer can be detected if a rise in the thyroglobulin level is found on monitoring. All patients who have undergone total thyroidectomy and those who have had radioactive ablation of any remaining thyroid tissue should be treated with thyroid hormone suppression. Individualize the degree of suppression to avoid complications such as subclinical hyperthyroidism.

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. [35]

A patient who has had a thyroidectomy without parathyroid preservation will require lifelong vitamin D and calcium supplementation.

More specific treatment information for FTC can be found at the National Comprehensive Cancer Network website, in the NCCN Clinical Practice Guidelines in Oncology section.

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. [36]

Previous