Thyroid cancer is the ninth most common malignancy in the U.S. At the time of diagnosis, thyroid cancer is mostly confined to the thyroid gland and regional lymph nodes. However, around 4% of patients with thyroid cancer present with metastatic disease. When compared with localized and regional thyroid cancer, 5-year survival rates for metastatic thyroid cancer are significantly worse (99.9%, 97.6%, and 54.7%, respectively). 1 Treatment options for metastatic thyroid cancer are limited and largely depend on the pathology and the type of thyroid cancer.
Thyroid cancer can be divided into differentiated, medullary, and anaplastic subtypes based on pathology. The treatment for metastatic differentiated thyroid cancer (DTC) consists of radioactive iodine therapy, thyroid-stimulating hormone (TSH) suppression (thyroxine hormone) therapy, and external beam radiotherapy. Systemic therapy is considered in patients with metastatic DTC who progress despite the above treatment modalities. In the case of metastatic medullary thyroid cancer (MTC), patients who are not candidates for surgery or radiation are considered for systemic therapy, because MTC does not respond to radioactive iodine or TSH suppressive therapy. On the other hand, metastatic anaplastic thyroid cancer is a very aggressive subtype with no effective therapy available to date. Palliation of symptoms is the main goal for these patients, which can be achieved by loco-regional resection and palliative irradiation. 2,3
This review focuses on the newer treatment options for metastatic DTC and MTC that are based on inhibition of cellular kinases.
Differentiated Thyroid Cancer
Differentiated thyroid cancer is the most common histologic type of thyroid cancer, accounting for 95% of all thyroid cancers and consists of papillary, follicular, and poorly differentiated thyroid cancer. 2,3 Surgery is the treatment of choice for DTC. Based on tumor size and its local extension in the neck, treatment options include unilateral lobectomy and isthmectomy, total thyroidectomy, central neck dissection, and more extensive resection. 2,3 After surgery, radioactive iodine is recommended in patients with known metastatic disease; locally invasive tumor, regardless of size; or primary tumor > 4 cm, in the absence of other high-risk features.2 This should be followed by TSH suppressive hormone therapy. 2
About 7% to 23% of patients with DTC develop distant metastases. 4 Two-thirds of these patients become refractory to radioactive iodine. 5 Prognosis remains poor in these patients, with a 10-year survival rate from the time detection of metastasis of only 10%. 5-7 Treatment options are limited. However, recently the understanding of cell biology in terms of key signaling pathways called kinases has been elucidated. The kinases that can stabilize progressive metastatic disease seem to be attractive therapeutic targets in treating patients whose disease no longer responds to radioiodine and TSH suppressive hormone therapy.
Papillary thyroid cancers frequently carry gene mutations and rearrangements