Refractory Thyroid Cancer: A Paradigm Shift in Treatment Is Not Far Off

Oncology 1,2 is noteworthy, even without further elaboration. Why has there been limited interest in developmental therapeutics for thyroid malignancies in the past? Much has to do with the natural history of thyroid carcinomas, traditional management paradigms, and the limitations of available chemotherapies. More than 90% of thyroid malignancies are derived from the thyroid follicular cell. The vast majority are differentiated tumors, with the papillary subtype predominating (approximately 80%); most of the remainder are follicular carcinomas and related variants. For these differentiated tumors, standard treatment with primary surgery and thyroidstimulating hormone (TSH) suppression with supraphysiologic thyroid hormone administration often suffices. Depending on disease stage, patient age, and a variety of histopathologic factors, ablation of the thyroid remnant with radioactive iodine 131 (RAI) is added. 3 This collective strategy is associated with an overall survival rate of approximately 90% at 20 years. 4 The prognosis remains relatively favorable even among patients who experience relapse, as the annual mortality rate is far less than the annual rate of recurrence. 5 Indeed, many patients with recurrent disease, even when incurable, will have an indolent course over months to years, with few or no symptoms without active anticancer therapy beyond TSH suppression. At relapse, further surgery, repeat RAI, external-beam radiation, or even observation with continued TSH suppression have all been commonly prioritized before chemotherapy. Drugs such as doxorubicin (the only United States Food and Drug Administration–approved agent), cisplatin, or bleomycin—administered as single agents or as part of some combination regimen— benefit a minority of patients, and related toxicities may be significant. 6-8