Appropriate surgical resection of the primary tumor and involved locoregional lymph nodes remains the mainstay of therapy for patients with thyroid cancer. Depending on the specific tumor histology and the estimated risk of recurrence/death, additional adjuvant therapies, such as radioactive iodine, levothyroxine suppression, or external beam irradiation, are often recommended. With these treatments, most patients with thyroid cancer can expect more than 90 percent disease-specific survival rates over a thirty-year follow-up period.

However, there is a subset of thyroid cancer patients with RAI refractory disease that can have survival rates as low as 30 percent over three to five years. Unfortunately, radioactive iodine (RAI)-refractory metastatic thyroid cancer has proven to be quite resistant to traditional cytotoxic chemotherapy. However, recent advances in our understanding of the molecular biology of thyroid cancer coupled with the availability of relatively specific tyrosine kinase inhibitors has dramatically changed our approach to the management of RAI-refractory, structurally progressive thyroid cancer.

In this chapter we review the initial presentation, risk stratification, and therapy of thyroid cancer with a specific emphasis on novel systemic therapy options for patients with structurally progressive disease that cannot be controlled with either local measures or RAI therapy.

PATTERNS OF METASTATIC SPREAD, ORGAN SPECIFICITY, TIMING OF RECURRENT DISEASE, AND COMPLICATIONS CONFRONTED WITH METASTASIS

Thyroid cancers arise either from thyroid follicular cells (papillary, follicular, and anaplastic thyroid cancers) or from other cells within the thyroid gland, such as lymphocytes (primary thyroid lymphoma) or neuroendocrine c-cells (medullary thyroid cancer).