While surgery is generally the treatment of choice for most thyroid cancers, there are several other treatment types that may be used in combination with surgery in order to achieve the best outcome for patients.
Adjunctive Therapy Treatments
Hormonal Therapy/TSH Suppression
Thyroid hormones are produced by the thyroid gland, and are crucial in the development of children, as well as in the metabolism of adults. Thyroid hormones must be available in certain quantities in order for the body to grow and function properly. A lack of these hormones can cause a variety of symptoms that can negatively affect a patient’s quality of life.
Hormonal Therapy
After undergoing thyroid surgery, patients will lose some, if not all of their thyroid gland, and may require thyroid hormone therapy in order to replace the thyroid hormones that their thyroid gland used to produce. All patients undergoing total thyroidectomy (complete removal of the thyroid gland) will require life-long hormone replacement therapy, as they will no longer be able to produce any thyroid hormone naturally. Hormone replacement therapy will be necessary to ensure normal metabolic function in these patients. For patients undergoing hemithyroidectomy (in which only some of the thyroid gland is removed), the decision about whether to undergo thyroid hormone replacement therapy will be made based on the patient’s thyroid blood tests, among a variety of other factors.
TSH Suppression
In addition to the replacement of the normal levels of thyroid hormones, most patients will be prescribed a higher-than-needed dose of synthetic thyroid hormone (generally Levothyroxine, T4), as this dosing can actually help to prevent recurrence of thyroid cancer.
This works through a complex feedback loop between the thyroid and the brain, involving thyroid hormone (T3 and T4) and another hormone called TSH (Thyroid Stimulating Hormone). TSH is a hormone produced in the pituitary gland in the brain that is responsible for stimulating the thyroid tissue to grow, absorb iodine from the body, and produce thyroid hormones. When thyroid hormone levels are low, the pituitary gland produces more TSH, which tells the thyroid to produce more thyroid hormone. When thyroid hormone levels are high, the pituitary gland stops producing TSH.
High levels of TSH can be dangerous for thyroid cancer patients because TSH stimulates the growth of thyroid tissue, which could increase the chances of a cancer recurrence. Taking high doses of synthetic thyroid hormone (Levothyroxine) tricks the pituitary gland into thinking that enough hormone is being produced, causing the pituitary to stop or reduce the production of TSH. Having low levels of circulating TSH helps prevent any remaining tissue after surgery from growing back and causing a possible recurrence.
Who Needs TSH Suppression?
TSH suppression therapy is used in many thyroid cancer patients in order to prevent recurrence of thyroid cancer.
- Patients with a high risk of recurrence are almost always advised to undergo TSH suppression therapy.
- Patients with a low or intermediate risk of recurrence may also benefit from TSH suppression, but there is not as much evidence to support this recommendation.
Low, Intermediate and High Risk Papillary Thyroid Cancers
Low Risk
| No local or distant metastases. |
| All macroscopic tumor has been resected. |
| No invasion of locoregional tissues ( cervical lymph nodes , strap muscles, etc). |
| Tumor was not found to have aggressive histologic variant*. |
| No vascular invasion. |
| No 131I uptake outside the thyroid bed on the post treatment scan, if done. |
| No evidence of suspicious lymph node extension in the neck or < 5 positive lymph nodes with size <0.2 cm in their largest dimension. |
Intermediate Risk
| Microscopic invasion into the perithyroidal soft tissues. |
| Cervical lymph node metastases or 131I avid metastatic foci in the neck on the post-treatment scan done after thyroid remnant ablation. |
| Tumor with aggressive histology* or vascular invasion. |
| Evidence of positive lymph node extension in the neck or > 5 positive lymph nodes with size <3 cm in their largest dimension. |
| Multifocal papillary thyroid microcarcinoma with extrathyroidal extension and BRAF V600E mutation (if known). |
High Risk
| Macroscopic tumor invasion. |
| Incomplete tumor resection with gross residual disease. |
| Distant metastases. |
| Postoperative serum thyroglobulin suggestive of distant metastases. |
| Evidence of positive lymph node extension with any lymph node >3 cm in their largest dimension. |
| Follicular thyroid cancer with extensive vascular invasion ( <4 foci of vascular invasion). |
In general, tumors with aggressive histology have a higher risk of recurrence. These features will be identified on pathologic evaluation.
List of Aggressive Histologic Variants of Papillary Thyroid Cancer
| Tall cell variant of papillary thyroid carcinoma. |
| Insular variant of papillary thyroid carcinoma. |
| Columnar cell variant of papillary thyroid carcinoma. |
| Hürtle cell carcinoma. |
| Follicular thyroid carcinoma. |
| Hobnail variant of papillary thyroid carcinoma. |
Side Effects
Doses of thyroid hormone large enough to suppress TSH production may cause additional side effects. These may include anxiety, weakness, weight loss, rapid and irregular heart beat, and bone loss. These effects are generally more severe in older patients.
Patients with existing bone or cardiac problems must be carefully screened and managed in order to be considered for TSH suppression therapy. Doctors will evaluate a patient’s TSH level, along with other clinical factors, in order to determine the optimal thyroid suppression levels for each individual patient, and should discuss the risks and benefits of this treatment with their patients.
It is important to remember that target TSH ranges may need to be modified in patients who have other conditions such as osteoporosis, osteopenia, and heart disease. This is because the negative side effects associated with TSH suppression have the potential to cause harmful effects on the bones and heart.
If a patient experiences heart related conditions, or a change in his or her bone status (detected on a bone density test), then the physician should be notified so that the adjustments can be made to the patient’s dosage of thyroid suppression medication.
Response to Therapy
Six to 12 months after a patient completes treatment for thyroid cancer, their doctor can assess the patient’s response to therapy in several ways:
- Measuring the levels of thyroglobulin in their blood.
- Performing an ultrasound exam of the neck.
- Potentially performing a radioactive iodine uptake scan.
Depending on how well the tumor responds to treatment, doctors may or may not adjust the patient’s target TSH level and the required dosing of thyroid hormone.
It is important to remember that patients at low risk for recurrence of thyroid cancer should keep TSH levels at or just below the lower limits of normal, depending on the advice of the patient’s endocrinologist or surgeon. For patients at high risk for recurrence of thyroid cancer and for those with persistent disease, TSH levels should be fully suppressed, unless suppression causes intolerable side effects. Patients who have a higher risk of recurrence, but appear to be disease free, should maintain TSH at the lower limits of normal or just below normal, depending on the advice of their endocrinologist and surgeon.
External Beam Radiation Therapy
While it remains the standard of care in many cancers of the head and neck, external beam radiation therapy is not often recommended for the treatment of thyroid cancer. For well-differentiated thyroid cancers, radioactive iodine therapy is preferred, because it is a more targeted form of radiation that attacks only thyroid cells and has fewer side effects. However, in select patients with aggressive cases of thyroid cancer that do not take up iodine and/or present with recurrent disease, adjuvant external beam radiation therapy may be considered.
Cases Where External Beam Radiation Therapy Might be Favored
- Patients who are over the age of 55 and have advanced T4 disease (gross extrathyroidal extension).
- Patients who have an aggressive cancer that cannot be completely resected surgically and is not sensitive to radioactive iodine.
- Patients who have distant metastases that are causing significant symptoms and cannot be surgically resected (spine, brain, thorax).
Radiation therapy uses high-energy radiation to shrink tumors and kill cancer cells. The radiation is delivered in the form of a beam of energy targeted directly at the tumor. The beam passes through the body and destroys the cancer cells in its path. Radiation kills cancer cells by directly damaging the cellular DNA, as well as by damaging the proteins and lipids that make up the cell wall and cellular structures.
Unfortunately, radiation therapy can also damage normal cells. However, modern techniques using computerized treatment planning allow the radiation specialist to more accurately focus the radiation on the cancer cells, minimizing the effects on surrounding normal tissues.
Systemic Therapies
Chemotherapy
Currently, very little research has been done on the use of chemotherapy as a treatment for well differentiated thyroid cancer. For patients who have persistent disease despite conventional treatments (such as surgery, TSH suppression therapy, and RAI), additional treatment options may include systemic chemotherapy. The goal of chemotherapy is to stabilize, or slow, the progression of metastatic disease. In other words, it attempts to prevent the disease from spreading throughout the body. Chemotherapy is considered a disease modifying drug because it is expected to stop disease progression, but results from clinical trials show that it does not improve overall survival or provide a cure.
Chemotherapy drugs can have significant side effects that vary according to the specific chemotherapeutic agent used and the administered dose. Therefore, it is important to limit the use of systemic treatments to only those patients who have very advanced disease and whose disease continues to progress despite all alternative treatment options.
Redifferentiation Therapy
A select group of patients who have progressive metastatic disease that has not responded to RAI therapy may benefit from a new group of drugs called redifferentiation therapies. These drugs focus on specific genetic mutations within cancer cells and target the cellular pathways affected by these mutations. These drugs are designed to inhibit “cancer-inducing” cellular changes, and thus stop the cancer from advancing. So far, there is no conclusive evidence that these drugs improve overall patient survival or quality of life.
Some examples of redifferentiation therapies include:
- Vascular Endothelial Growth Factor Receptors (VEGFRs)
These are growth factors that promote tumor growth and are highly expressed in patients with well-differentiated thyroid cancer. VEGFR-targeting drugs have shown promising activity in the treatment of advanced thyroid cancer. - Cancer-promoting Mutations
Mutations such as BRAF, RAS and RET. BRAF V600E have been identified as some of the most prevalent mutations in thyroid cancer. These mutations are known to translate to a worse prognosis. They are associated with a decreased response to RAI therapy, which is the principal adjunctive therapy used in well-differentiated thyroid malignancies. Several BRAF-inhibitors exist, and some are currently being studied to test their success in treating thyroid cancer.
