Treatment of Stage IV Thyroid Cancer

Treatment of stage IV - metastatic and recurrent Thyroid Cancer

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 9/2019

Stage IV thyroid cancer—also called metastatic disease is cancer that has spread beyond the thyroid to the soft tissues of the neck, lymph nodes in the neck, or distant locations in the body. The lungs and bone are the most frequent sites for distant spread. Papillary carcinoma more frequently spreads to regional lymph nodes than to distant sites. Follicular carcinoma is more likely to invade blood vessels and spread to distant locations. Anaplastic thyroid cancer is considered metastatic at diagnosis.

The prognosis for patients with distant metastases has historically been poor but the recent development of newer precision cancer medicines appears promising. Cancer treatment may consist of surgery, radioactive iodine treatment, radiation, chemotherapy, precision cancer medicines or a combination of these treatment techniques. Combining two or more of these treatment techniques has become an important approach for increasing a patient’s chance of cure and prolonging survival.

Metastatic or Recurrent Papillary or Follicular Thyroid Cancer

Treatment is usually a combination of treatment techniques including surgery to remove cancer and radioactive iodine treatment. Surgery for typically consists of removing the entire thyroid if it has not already been performed.

Radioactive Iodine Treatment; Research indicates that treatment with radioactive iodine improves survival for patients with thyroid cancer that has spread to nearby lymph nodes or to distant locations in the body. (1,2)

Metastatic disease that is radiation resistant is treated with systemic “chemotherapy” medications called multi-kinase inhibitors and precision cancer medicines.

Anaplastic and Medullary Thyroid Cancer

Anaplastic and medullary thyroid carcinoma are inherently non-sensitive to radioactive iodine treatment, (2) and require treatment with precision cancer medicines or participation in a clinical trial.

Systemic Therapy: Precision Cancer Medicine, Chemotherapy, and Immunotherapy

Systemic therapy is any treatment directed at destroying cancer cells throughout the body and consists of chemotherapy and precision cancer medicines. Chemotherapy has not been very effective but newer precision cancer medicines appear promising. (3-9)

Precision Cancer Medicines

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the thyroid cancer cells with specific abnormalities, leaving normal cells largely unharmed. (6-8)

Patients should discuss the role of genomic-biomarker testing for the management of their cancer with their treating oncologist.

Surgery

If patients with recurrent thyroid cancer have not already had their thyroid removed, they will likely undergo a total thyroidectomy to remove the rest of their thyroid and any other cancer in the neck region. Patients who have had their thyroid removed also often have recurrent cancer in the neck region and will undergo surgery to have as much of the cancer as possible removed.

Surgery to remove metastases: Surgery to remove metastases from thyroid cancer has been shown to benefit some patients. In a clinical trial, metastases from thyroid cancer were removed from the mediastinum (area behind the breast bone), lung, bone, kidneys, and brain of 29 patients with advanced thyroid cancer. All patients were also treated with multiple radioiodine treatments. External-beam radiation therapy, chemotherapy, and other measures to relieve symptoms of the cancer were used. (4)

Strategies to Improve Treatment

Iodine Resensitization: Radioactive iodine (RAI) is widely used in the treatment of advanced follicular cell-derived thyroid cancers, but patients may become develop radiation resistant disease. This occurs because of down regulation of the sodium-iodide symporter gene (SLC5A5, more commonly known as NIS).

Researchers have figured out how to turn or enhance “redifferentiation” of NIS so that: the cancer cells can be treated with radioiodine again. Retinoids, Selumetinib (a MEK inhibitor) and Dabrafenib (BRAF inhibitor) have been shown to restore RAI uptake in advanced patients. (10-12)

References:

  1. Podnos YD, Smith D, Wagman LD, Ellenhorn JD. Radioactive iodine offers survival improvement in patients with follicular carcinoma of the thyroid. Surgery. 2005;128(6):1072-6.
  2. Rosenbluth BD, Serrano V, Happersett L, et al. Intensity-modulated radiation therapy for the treatment of nonanaplastic thyroid cancer. International Journal of Radiation Oncology Biology Physics. 2005;63(5):1419-26.
  3. De Besi P, Busnardo B, Toso S, et al. Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. Journal of Endocrinology Investigation. 1991;14(6):475-80.
  4. Pak H, Gourgiotis L, Chang WI, et al. Role of metastasectomy in the management of thyroid carcinoma: the NIH experience. Journal of Surgical Oncology. 2003;82(1):10-8.
  5. Schlumberger M, Makoto T, Wirth L, et al. The New England Journal of Medicine; 372:621-630 February 12, 2015.
  6. Brose MS, Sherman SI, Schöffski P, et al. Correlative analyses of RET and RAS mutations in a phase III study of cabozantinib in patients with progressive, metastatic medullary thyroid cancer. Presented at the 83rd Annual Meeting of the American Thyroid Association, October 16- 20, 2013, in San Juan, Puerto Rico. Thyroid. October 2013, 23(S1): A-1-A-114. Abstract 4.
  7. FDA approves Nexavar to treat type of thyroid cancer. [FDA News Release]. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376443.htm
  8. Advanced Thyroid Cancer Responds to Targeted Therapy with Sunitinib [press release]. Endocrine Society website. Available at: https://www.endocrine.org/news-room/current-press-releases/advanced-thyroid-cancer-responds-to-targeted-therapy-with-sunitinib.
  9. De Besi P, Busnardo B, Toso S, et al. Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. Journal of Endocrinology Investigation. 1991;14(6):475-80.
  10. Kogai T, Brent GA. The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics. Pharmacol Ther. 2012;135(3):355–370. doi: 10.1016/j.pharmthera.2012.06.007.[
  11. Ho AL, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013;368(7):623–632. doi: 10.1056/NEJMoa1209288.
  12. Rothenberg SM, et al. Redifferentiation of iodine-refractory <em>BRAF</em> V600E-mutant metastatic papillary thyroid cancer with Dabrafenib. Clin Cancer Res. 2015;21(5):1028–1035. doi: 10.1158/1078-0432.CCR-14-2915.
Comments