Treatments: Thyroid Cancer and Suspected Thyroid Cancer
Commonly, the thyroid gland has one or more lumps in it, which are called nodules. The vast majority of these nodules are benign. While most benign nodules do not require any treatment, some of the benign nodules do when they are producing too much thyroid hormone or are compressing nearby anatomy. While only about 5% of all nodules harbor cancer, the large number of people with thyroid nodules makes thyroid cancer moderately prevalent in the population. Fortunately, most types of thyroid cancer are not particularly aggressive and the cure rate is high. When a nodule is identified, its risk is assessed and additional management steps are undertaken with a focus on choosing the best treatment for each individual situation. Surgery plays a central role in the definitive assessment of a suspicious thyroid nodule and in treatment of thyroid cancer. Other modalities of treatment are generally supplementary.
Evaluation prior to treatment and extent of planned surgery
Prior to surgical removal of a thyroid nodule, the degree of certainty regarding the nature of the nodule is not always certain. Usually, the evaluation of a thyroid nodule found to be suspicious by diagnostic ultrasound involves ultrasound guided fine needle aspiration biopsy. From this biopsy, the pathologist’s will ideally categorize the nodule according to the Bethesda classification, which essentially gives a percentage likelihood that a nodule is cancer, and it may indicate which type of cancer. Sometimes, the likelihood of cancer based on a needle biopsy is very high, and other times it is not.
Final and definitive diagnosis for a suspicious thyroid nodule is rendered by a pathologist who has had the entire nodule removed surgically. Prior to surgery and with best use of the available data, the patient and the surgeon decide upon a plan, which may involve partial thyroidectomy (removing the lobe containing the nodule of concern) or a total thyroidectomy (removing all of the thyroid gland).
When a partial thyroidectomy is undertaken, the definitive pathology report is issued about 1-2 weeks later. The pathology report contains the specific diagnosis, whether the nodule is cancerous or not, and if so, which type of thyroid cancer. When cancer is identified, the report will also detail which, if any, high risk factors are present. Based on this pathologic data, which is more informative than results from a needle biopsy, a decision may be made regarding the need for further treatment, such as another operation to remove the remaining lobe, and then, once all visible thyroid tissue is removed, possible radioactive iodine ablation.
Another strategy is to undertake a total thyroidectomy upfront. When this is done, the pathology report issued 1-2 weeks after surgery may confirm the presence of thyroid cancer. It may also indicate the presence of risk factors that indicate the need for all of the thyroid gland to be removed. In this case, the strategy of removing the entire thyroid upfront has paid off and the patient is spared a second operation for completion thyroidectomy had a partial thyroidectomy been undertaken initially. Another potential outcome of undertaking total thyroidectomy upfront is that the final pathology report indicates the absence of cancer in the now-removed thyroid gland.
Thus, decision-making for the extent of surgery is a matter of weighing risks and benefits along with a patient’s personal preference. Ongoing research has provided surgeons with many insights that can assist with recommendations for the extent of surgery.
Removal of the thyroid gland (total thyroidectomy)
Total thyroidectomy is a surgical procedure to remove all thyroid tissue that can be seen. Although this involves removing the entire gland from a gross structural standpoint, it is well known that some thyroid cells typically remain behind. Patients with normal parathyroid anatomy, meaning having four glands, all in close relationship to the thyroid, may experience low parathyroid gland output following thyroidectomy. If this occurs, it is usually temporary, with a reported rate of permanently low parathyroid hormone (hypoparathyroidism) being around 2%. Also with total thyroidectomy is the dissection of thyroid from the recurrent laryngeal nerves and the superior laryngeal nerves on each side. Temporary hoarseness after thyroid surgery is commonly related to the breathing tube placed between the vocal cords, but long-term hoarseness due to weakness of one or both vocal cords is thought to be about 2%. If that were to occur, there are procedures available to improve the voice, such as vocal cord injection medialization or medialization thyroplasty. When the entire thyroid gland has been removed, replacement of thyroid hormone is needed, and this is in the form of one pill per day taken on an empty stomach.
Removal of part of the thyroid gland (Partial thyroidectomy)
A procedure in which less than all of the thyroid is removed is called a partial thyroidectomy. Usually, this takes the form of hemithyroidectomy and isthmusectomy. Removing just the nodule of concern would seem to make sense, but is not done for several reasons that come down to risk and benefit. By leaving the remaining thyroid lobe undissected, the parathyroid glands on that side and the laryngeal nerves on that side (recurrent laryngeal nerve and external branch of superior laryngeal nerve) are not at risk. Further, the remaining thyroid lobe may be able to produce all the thyroid hormone the body needs. If it cannot, supplemental thyroid hormone in pill form is used.
Removal of lymph nodes (cervical lymphadenectomy or “neck dissection”)
Thyroid cancers have the ability to spread to lymph nodes of the neck. Papillary thyroid carcinoma is especially prone to spreading to lymph nodes, whereas follicular thyroid carcinoma is less prone to spread to lymph nodes and relatively more likely to spread by blood to a tissue such as the lung. When thyroid cancer is suspected, ultrasound evaluation of the side of the neck can be undertaken to identify any suspicious neck lymph nodes. If found, typically ultrasound guided fine needle aspiration biopsy of one or more suspicious lymph nodes is undertaken. The pathologist’s reading of the needle biopsy is used in the decision-making for extent of surgery. If one or more lymph nodes appears to have cancer spread to it, the surgical approach normally involves removing the entire thyroid gland and the lymph nodes in the region of the known cancerous (“positive”) lymph node. This procedure, when done is skilled and experienced hands, can remove cancerous lymph nodes with maximal preservation of the important nerves, muscles, and blood vessels in the neck.
Radioactive iodine ablation
Radioactive iodine damages thyroid tissue. It cannot eliminate an entire thyroid gland, but it can shrink and slow activity of a thyroid gland, and it can often eliminate any microscopic collections of thyroid cells after a total thyroidectomy.
Iodine with an atomic mass of 131 breaks down at a steady rate to a more stable element, 131-Xenon. In this process, it emits an electron. When given in pill or liquid form by mouth, 131-Iodine is absorbed by the gut, circulates in the blood, and then collects in the one tissue that takes up iodine—thyroid tissue. That is, wherever in the body that there is thyroid tissue, as long as it is still acting like thyroid tissue, it will take up and concentrate the circulating iodine. This allows the electrons generated by radioactive decay to be distributed very selectively to thyroid cells, whether in the thyroidectomy bed, or an area of thyroid cancer spread, such as a lymph node or the lungs. The electrons emitted by the decaying 131-iodine kill the surrounding cells, but since these electrons travel a very short distance (about 2 mm), the surrounding non-thyroid tissue receives virtually no radiation at all! This clever treatment technique works when thyroid tissue is iodine avid, meaning it takes up iodine quickly and in high quantities. To make iodine-avid thyroid tissue maximally avid, a patient is either allowed to become temporarily hypothyroid (which increases TSH production, stimulating thyroid cell activity) or recombinant (synthetic) TSH is given intravenously shortly before the 131-iodine is given. This strategy works only when there is no more thyroid gland present (because even a remaining thyroid lobe would soak up so much of the 131-iodine as to leave an insufficient amount to treat any cancer metastases) AND when the thyroid cancer has not mutated so much that it no longer acts like it’s mother tissue and no longer takes up iodine.
TSH suppression using oral thyroid hormone
Keeping the concentration of thyroid stimulating hormone (TSH) low is a strategic method of lowering the chance of thyroid tissue from growing. In the context of thyroid cancer when the thyroid gland has been removed, the possibility of even tiny numbers of cancerous thyroid cells remaining in the body is reason to try not to encourage their growth.
TSH makes thyroid tissue more active. To a normal thyroid gland, contact with circulating TSH would cause increased activity and thyroid hormone production. When a thyroid gland is not producing enough thyroid hormone, increased TSH production is the body’s way to get the thyroid gland to produce more thyroid hormone. And when there is an excess of thyroid hormone in circulation, the pituitary gland produces less thyroid hormone, signaling a decrease in thyroid hormone production by the thyroid gland. In the case of thyroid cancer, TSH is also a stimulus for growth of the thyroid cancer cells, not just to make more thyroid hormone, but to become a more active cancer. For this reason, after surgical and possibly radioactive iodine treatment for thyroid cancer, keeping the TSH level reasonably low may be desirable. The way to keep TSH low is to give just enough thyroid hormone medication (usually with a daily pill of levothyroxine) to meet and slightly exceed the body’s need. This replicates a situation of an over-active thyroid gland as described above, and any potential thyroid tissue (cancer or non-cancer) remaining in the body will have expodure to less TSH to stimulate growth. Recent guidelines do not recommend thyroid-stimulating hormone (TSH) suppressive therapy with levothyroxine for benign nodules because the nodule shrinking effect is uncertain but may result in hyperthyroidism side effects such as long-term osteoporosis (weak bones) or atrial fibrillation (an irregular heart rhythm). For cancers, the benefits of TSH suppression may be worth these risk.
Immunotherapy
Immunotherapy is emerging as a promising treatment for thyroid cancer, particularly for advanced or metastatic thyroid cancer, and for iodine refractory thyroid cancer. This approach harnesses the body's immune system to target and destroy cancer cells. Drugs that block growth of blood vessels (e.g., lenvatinib) are a common immunotherapy strategy for advanced thyroid cancer. One additional key immunotherapy strategies involves immune checkpoint inhibitors, which work by blocking the mechanisms that cancer cells use to evade the immune system. More recently, the FDA has approved certain immunotherapy drugs to be used when a specific mutation exists within a thyroid cancer. Ongoing research and clinical trials are continuously expanding our understanding of how immunotherapy can be effectively utilized in the treatment of thyroid cancer.
External Beam Radiation Therapy
Radiation therapy, delivered by a beam directed through the skin, may be of benefit in some circumstances for thyroid cancer. External beam radiotherapy is not a first-line treatment choice for most thyroid cancers because it is generally not as effective on thyroid cancers as other modalities of treatment. It may prove to be of some benefit in certain situations, however, especially when other treatment options have already been used or are not available.
Percutaneous ethanol injection (PEI)
Percutaneous ethanol injection is the direct injection of ethanol through a needle or a catheter for the purpose of atrophy of a benign and predominantly cystic (having >50% fluid content) thyroid nodule causing symptoms such as a neck bulge or pressure. It is not typically used for cancerous nodules, and follow-up on a nodule treated with PEI is necessary to watch for signs it may be malignant. Recently, PEI has been advocated for use in highly selected thyroid cancers in special circumstances in which surgery is not an option (if the patient is not healthy enough for general anesthesia, for example). Larger nodules require repeated treatments.
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