Medullary thyroid cancer is a rare form of thyroid cancer that originates from special cells within the thyroid gland. Though uncommon, with about 1,000 new cases diagnosed each year in the United States, understanding its treatment options—from surgery to emerging targeted therapies—can make a significant difference in managing this disease.

Treating a Rare Form of Thyroid Cancer: What You Need to Know

Medullary thyroid cancer, often called MTC, represents a unique challenge in the world of thyroid diseases. Unlike the more common forms of thyroid cancer that develop from cells producing thyroid hormone, MTC comes from parafollicular C cells—specialized cells that produce a hormone called calcitonin, which plays a role in calcium regulation in the body. Because this cancer behaves differently from other thyroid cancers, the treatment approach must be tailored specifically to its characteristics.^[1]

The main goal of treating medullary thyroid cancer is to remove all cancer tissue from the body whenever possible, prevent the disease from spreading to other organs, control symptoms when the cancer has advanced, and help patients maintain the best possible quality of life. The treatment path depends heavily on several factors: how far the cancer has spread at the time of diagnosis, whether it’s confined to the thyroid gland or has moved to nearby lymph nodes, whether it has reached distant organs like the lungs or liver, and whether the patient has a hereditary form of the disease or a sporadic case that developed without a family history.^[2]

About 75% of medullary thyroid cancer cases are sporadic, meaning they occur randomly without a known genetic cause. The remaining 25% are hereditary, linked to genetic mutations that can be passed down through families. In hereditary cases, the cancer may be part of syndromes called multiple endocrine neoplasia type 2 (MEN2), which can affect other hormone-producing glands as well. Understanding whether the cancer is sporadic or hereditary influences not only treatment decisions but also whether family members should be tested for genetic mutations.^[6]

Standard Surgical Treatment: The Foundation of Care

Surgery remains the cornerstone of medullary thyroid cancer treatment and offers the only potential cure, especially when the cancer is detected before it spreads beyond the thyroid gland. The primary surgical procedure is called a total thyroidectomy, which involves complete removal of the thyroid gland. This comprehensive approach is necessary because medullary thyroid cancer can develop in multiple locations within the thyroid, and leaving any thyroid tissue behind could allow cancer to persist or return.^[4]

Most patients also require removal of lymph nodes in the neck during the same operation, a procedure known as neck dissection or lymph node dissection. The extent of lymph node removal depends on the size of the tumor and whether imaging studies suggest cancer has spread to the lymph nodes. Studies show that 70% of patients already have lymph node involvement at the time of diagnosis, which makes this component of surgery particularly important. The surgeon may remove lymph nodes from the central compartment of the neck (the area directly around the thyroid) and sometimes from the lateral compartments (the sides of the neck) if cancer has spread more extensively.^[3]

The surgery typically requires a hospital stay and is performed under general anesthesia. The surgeon makes an incision across the lower front of the neck to access the thyroid gland. During the procedure, great care must be taken to protect important structures nearby, including the recurrent laryngeal nerves that control the vocal cords and the parathyroid glands that regulate calcium levels in the blood. Damage to these nerves can cause voice changes or hoarseness, while removal or damage to the parathyroid glands can lead to low calcium levels that require supplementation.^[5]

For patients with hereditary forms of medullary thyroid cancer who carry known genetic mutations, preventive surgery may be recommended before cancer develops. This is particularly true for patients with MEN2B, who have a 100% chance of developing medullary thyroid cancer at a very young age. In these cases, removing the thyroid gland early—sometimes even in childhood—can prevent cancer from ever forming. Genetic counseling plays a crucial role in helping families understand these options and make informed decisions.^[1]

After a total thyroidectomy, patients will need lifelong thyroid hormone replacement therapy with a medication called levothyroxine. This synthetic hormone replaces the thyroid hormone that the body can no longer produce. Patients take one pill daily, and their doctor monitors blood levels regularly to ensure the dose is correct. Unlike with some other thyroid cancers, the goal is simply to replace normal thyroid hormone levels, not to suppress thyroid-stimulating hormone to prevent cancer recurrence.^[14]

Possible side effects and complications from thyroid surgery can include temporary or permanent voice changes if the nerves controlling the vocal cords are affected, low calcium levels requiring supplements if the parathyroid glands are damaged or removed, bleeding or infection at the surgical site, and the development of a scar across the lower neck (though surgeons use techniques to minimize scarring). Most patients recover well from surgery and can return to normal activities within a few weeks, though heavy lifting and strenuous exercise should be avoided during the initial healing period.^[17]

Monitoring and Follow-Up After Surgery

After surgery, careful monitoring is essential to detect any remaining cancer or recurrence as early as possible. Doctors use blood tests to measure levels of calcitonin and another marker called carcinoembryonic antigen (CEA), both of which are typically elevated in patients with medullary thyroid cancer. These levels should drop dramatically after successful surgery. If they remain elevated or begin to rise again, it suggests that cancer cells remain in the body or that the cancer has returned.^[18]

Regular imaging studies, including ultrasound of the neck, CT scans, or MRI, may be performed to look for any signs of cancer recurrence in the neck or spread to distant organs. The frequency of these tests depends on the initial extent of disease and how well the calcitonin and CEA levels responded to surgery. Patients with completely normal tumor markers after surgery and no evidence of remaining disease may need less frequent monitoring than those with persistently elevated levels.^[15]

Treatment Options When Cancer Persists or Returns

Unfortunately, not all medullary thyroid cancer can be completely removed with surgery, and in some cases the cancer returns after initial treatment. When cancer persists after surgery or comes back (recurs), the treatment approach depends on several factors: where the cancer is located, how quickly it is growing, whether it is causing symptoms, and the patient’s overall health. Many patients with persistent disease have cancer that grows very slowly and may not cause problems for years, while others have more aggressive disease that requires active treatment.^[11]

For patients with small amounts of remaining disease that is growing slowly (generally increasing in size by less than 20% per year), doctors may recommend careful monitoring rather than immediate additional treatment. This approach, sometimes called “watchful waiting” or “active surveillance,” involves regular imaging and blood tests every 6 to 12 months to track how the cancer behaves. Treatment is reserved for cases where the disease begins to progress more rapidly or causes symptoms. This strategy acknowledges that aggressive treatment isn’t always necessary or beneficial, especially for slow-growing disease.^[11]

When cancer recurs in the neck and can be seen on imaging studies, additional surgery may be an option to remove the recurrent tumor and any involved lymph nodes. This is most successful when the recurrence is localized to a specific area that can be completely removed. However, repeated neck surgeries carry higher risks of complications, particularly injury to the nerves controlling the voice and damage to the parathyroid glands.^[24]

External beam radiation therapy may be considered in certain situations, particularly when cancer has spread extensively in the neck, when surgical margins were positive (meaning cancer cells were found at the edge of the removed tissue), or when cancer cannot be completely removed with surgery. Radiation involves directing high-energy beams at the cancer to kill cancer cells or slow their growth. While medullary thyroid cancer is generally less responsive to radiation than some other cancers, radiation can help with local control and may provide symptom relief, particularly for cancer that has spread to bones and is causing pain.^[14]

Innovative Therapies Being Tested in Clinical Trials

The landscape of medullary thyroid cancer treatment has been transformed in recent years by the development of targeted therapies—medications that specifically attack cancer cells by interfering with molecules and pathways that the cancer needs to grow and spread. These medications represent a major advance, particularly for patients with advanced or metastatic disease that cannot be controlled with surgery or radiation.^[12]

Two medications called vandetanib and cabozantinib have been approved for treating advanced medullary thyroid cancer based on results from Phase III clinical trials. These drugs belong to a class called tyrosine kinase inhibitors (TKIs) or multi-kinase inhibitors. They work by blocking multiple proteins that cancer cells use to grow, divide, and form new blood vessels to supply tumors with nutrients.^[15]

Vandetanib blocks several different targets, including proteins involved in tumor growth and blood vessel formation. In clinical trials, patients taking vandetanib experienced longer periods before their cancer progressed compared to patients taking placebo. The medication is taken as a daily pill and has been shown to slow disease progression in many patients with advanced medullary thyroid cancer. Common side effects include diarrhea, rash, high blood pressure, nausea, and fatigue. One important side effect that requires monitoring is the potential to affect the electrical activity of the heart, which can be detected with an electrocardiogram.^[12]

Cabozantinib works similarly by blocking multiple tyrosine kinases involved in tumor growth and the formation of new blood vessels. Clinical trials demonstrated that cabozantinib could prolong the time before cancer progression in patients with progressive, metastatic medullary thyroid cancer. Like vandetanib, it is taken as a daily pill. Side effects include diarrhea, hand-foot syndrome (redness, swelling, and pain on the palms and soles), decreased appetite, weight loss, nausea, and fatigue. High blood pressure and effects on wound healing are also concerns with this medication.^[12]

More recently, a new generation of even more targeted therapies has been developed. These are called selective RET inhibitors because they specifically target the RET protein, which is altered in nearly all hereditary medullary thyroid cancers and in about 40-50% of sporadic cases. Two medications in this class—selpercatinib and pralsetinib—have shown remarkable results in clinical trials.^[15]

Selpercatinib was studied in Phase I and II clinical trials that included patients with RET-mutant medullary thyroid cancer. The results were striking: a high percentage of patients experienced significant tumor shrinkage, and many achieved responses that lasted for extended periods. Because selpercatinib is more selective for the RET protein, it tends to have fewer side effects than the older multi-kinase inhibitors. Common side effects include elevated liver enzymes, dry mouth, diarrhea, high blood pressure, and fatigue, but these are often manageable. In the United States, selpercatinib has been approved for adults and children aged 2 years or older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy.^[11]

Pralsetinib is another selective RET inhibitor with a similar mechanism of action. Clinical trials have demonstrated its effectiveness in shrinking tumors in patients with RET-mutant medullary thyroid cancer. Like selpercatinib, pralsetinib tends to have a more favorable side effect profile than older, less selective medications. The most common side effects include elevated liver enzymes, constipation, fatigue, and changes in blood counts. Both of these selective RET inhibitors represent an important advance because they are more targeted, potentially more effective, and generally better tolerated than earlier therapies.^[15]

Patients who don’t have RET mutations or who cannot tolerate or do not respond to RET inhibitors may be treated with other tyrosine kinase inhibitors. Medications such as sorafenib and sunitinib, though not specifically approved for medullary thyroid cancer, have shown some activity in clinical studies and may be options in certain circumstances. These drugs also work by blocking multiple proteins involved in cancer growth and blood vessel formation.^[11]

For patients whose disease progresses despite targeted therapy, or who cannot participate in clinical trials, traditional chemotherapy may be considered. Various chemotherapy regimens have been tested, often combining drugs like dacarbazine with other agents such as vincristine, 5-fluorouracil, cyclophosphamide, streptozocin, or doxorubicin. However, chemotherapy has generally shown limited effectiveness in medullary thyroid cancer, and no single regimen has proven clearly superior to others. Response rates are typically modest, and chemotherapy is usually reserved as a later option when other treatments are not suitable.^[11]

Researchers continue to explore new treatment approaches in ongoing clinical trials. Some experimental therapies being investigated include peptide receptor radionuclide therapy, which uses radioactive substances attached to molecules that bind to receptors on tumor cells, delivering targeted radiation directly to cancer cells. Other trials are testing combinations of different targeted therapies or combining targeted therapy with immunotherapy—treatments that help the immune system recognize and attack cancer cells. Participating in clinical trials gives patients access to promising new treatments before they become widely available and contributes to advancing knowledge that benefits future patients.^[11]

Clinical trials for medullary thyroid cancer are being conducted at medical centers across the United States, Europe, and other regions. Eligibility for trials depends on factors such as the extent of disease, prior treatments, overall health, and sometimes whether the cancer has specific genetic mutations. Patients interested in clinical trials should discuss this option with their oncologist, who can help identify appropriate studies and explain what participation would involve.^[2]

Most common treatment methods

• Surgery
  • Total thyroidectomy: Complete removal of the thyroid gland, which is the standard surgical approach for medullary thyroid cancer
  • Neck dissection: Removal of lymph nodes in the neck to eliminate cancer that has spread beyond the thyroid
  • Preventive thyroidectomy: Removal of the thyroid gland before cancer develops in patients with known genetic mutations that cause hereditary medullary thyroid cancer
• Hormone replacement therapy
  • Levothyroxine: A synthetic thyroid hormone taken daily as a pill to replace the hormones normally produced by the thyroid gland after thyroidectomy
• Radiation therapy
  • External beam radiation therapy: High-energy rays directed at areas of cancer to kill cancer cells, particularly useful for cancer that cannot be completely removed surgically or has spread to bones
• Targeted therapy with tyrosine kinase inhibitors
  • Vandetanib: A multi-kinase inhibitor that blocks several proteins involved in tumor growth and blood vessel formation, approved for advanced medullary thyroid cancer
  • Cabozantinib: Another multi-kinase inhibitor shown to slow disease progression in patients with progressive, metastatic medullary thyroid cancer
  • Selpercatinib: A selective RET inhibitor approved for RET-mutant medullary thyroid cancer, offering high response rates with generally better tolerability than older drugs
  • Pralsetinib: Another selective RET inhibitor with demonstrated effectiveness in shrinking tumors in patients with RET-mutant disease
  • Sorafenib and sunitinib: Additional tyrosine kinase inhibitors that may be used in certain situations, though not specifically approved for medullary thyroid cancer
• Chemotherapy
  • Various combinations typically including dacarbazine with other agents such as vincristine, 5-fluorouracil, cyclophosphamide, streptozocin, or doxorubicin, generally reserved for patients who cannot receive or do not respond to targeted therapy
• Experimental therapies in clinical trials
  • Peptide receptor radionuclide therapy: Uses radioactive substances attached to molecules that deliver targeted radiation directly to tumor cells
  • Combination treatments: Trials testing combinations of different targeted therapies or targeted therapy plus immunotherapy

Managing Side Effects and Quality of Life

Living with medullary thyroid cancer and its treatments requires ongoing attention to side effects and quality of life. Patients taking targeted therapy medications may experience a range of side effects that can affect daily activities. Diarrhea is one of the most common issues and can often be managed with dietary modifications, over-the-counter or prescription medications, and staying well hydrated. Skin problems such as rash or hand-foot syndrome may require special skin care, protective measures, and sometimes temporary dose reductions of the medication.^[12]

High blood pressure is a common side effect of many targeted therapies and requires regular monitoring and often treatment with blood pressure medications. Fatigue can be significant for some patients and may improve with adjustments to the medication dose, regular gentle exercise, good sleep habits, and strategies to conserve energy for important activities. Changes in appetite and weight loss may require working with a nutritionist to ensure adequate nutrition.^[12]

Regular communication with the healthcare team is essential for managing side effects effectively. Many side effects can be controlled with supportive medications, dose adjustments, or temporary breaks from treatment. Patients should never stop taking their medication without consulting their doctor, as this could allow the cancer to progress. On the other hand, reporting side effects promptly allows the medical team to intervene before problems become severe.^[15]

The emotional impact of living with medullary thyroid cancer should not be underestimated. Even though many patients have slow-growing disease with a favorable prognosis, the diagnosis of cancer and the need for lifelong monitoring and treatment can cause anxiety, stress, and worry about the future. Support groups, counseling, and connecting with other patients who have faced similar challenges can be valuable. Many hospitals and cancer centers offer support services, including social workers, psychologists, and patient navigator programs to help patients and families cope with the practical and emotional aspects of cancer care.^[17]

The Importance of Genetic Testing and Family Screening

All patients diagnosed with medullary thyroid cancer should be offered genetic testing to determine whether they have a hereditary form of the disease. This is important even if there is no known family history, as a patient could be the first in their family to be diagnosed. Testing looks for mutations in the RET proto-oncogene, which is responsible for virtually all cases of hereditary medullary thyroid cancer.^[6]

If a RET mutation is found, this has important implications not just for the patient but for their family members. Each child of a person with a hereditary RET mutation has a 50% chance of inheriting the mutation. Family members who test positive for the mutation can be offered preventive surgery to remove the thyroid before cancer develops, which can be curative. Family members who test negative do not need this intervention and can be reassured that they will not pass the mutation to their children.^[1]

Genetic counseling is an important part of this process. A genetic counselor can explain how genetic testing works, what the results mean, how to discuss testing with family members, and what options are available for mutation carriers. This specialized support helps families navigate complex medical and personal decisions about testing and prevention.^[17]

Looking Ahead: The Future of Treatment

The prognosis for patients with medullary thyroid cancer varies depending on the stage at diagnosis and how completely the cancer can be removed with surgery. For patients diagnosed with disease confined to the thyroid gland that can be completely removed, the outlook is generally very good. However, medullary thyroid cancer accounts for a disproportionate share of thyroid cancer deaths relative to its incidence, largely because of its tendency to spread to lymph nodes and distant organs and its resistance to radioactive iodine therapy.^[4]

The development of selective RET inhibitors represents a major breakthrough that is changing the treatment paradigm for advanced medullary thyroid cancer. These medications are providing hope for patients with progressive disease, offering meaningful tumor shrinkage and disease control with better tolerability than earlier options. As researchers better understand the molecular biology of medullary thyroid cancer, additional targeted approaches are likely to emerge.^[15]

Ongoing research is also focused on identifying biomarkers that can predict which patients are most likely to benefit from specific treatments, allowing for increasingly personalized treatment approaches. Better ways to monitor disease and predict progression are being developed, which may help guide decisions about when to start treatment and when careful observation is sufficient.^[12]