Radioiodine Refractory Differentiated Thyroid Cancer: Time to Update the Classifications

Background: The management of aggressive and progressing metastatic differentiated thyroid cancer (DTC) is very difficult, and the determination as to when such patients are refractory to ¹³¹I therapy (e.g., radioiodine refractory) is problematic and controversial.

Objective: The objective of this review is to discuss (i) the present major classifications of radioiodine refractory disease in DTC, (ii) factors that should be considered before designating a patient's DTC as radioiodine refractory, (iii) potential approaches and caveats to help manage and minimize a patient's exclusion from an ¹³¹I therapy that may have potential benefit in patients with aggressive and progressing metastatic DTC, (iv) next steps for revision of the classifications of radioiodine refractory DTC, and (v) areas for future research.

Summary: To date, the classifications of radioiodine refractory DTC, although very useful, are not sacrosanct especially in the context of individualized patient management, and merely because a patient meets one or more of the various classifications, one should not consider by definition, fiat, or de facto that that a patient's DTC is radioiodine refractory. Rather, each patient should be individually managed with a good understanding of the limitations of the various classifications and potential approaches to help manage that patient. With awareness of the suggestions and caveats discussed herein and with assessment of the many other factors that affect the patient's specific clinical situation, the managing physician can deliver appropriate individualized patient care. A multi-organizational committee should be established as a standing committee to supervise and assist in the update of the classifications of radioiodine refractory DTC, including discussions of their limitations.

Conclusion: Classifications to help determine radioiodine refractory disease will continue to evolve as (i) more studies are published, (ii) managing physicians better understand the limitations and confounding factors of present classifications, and (iii) new agents either increase or reestablish ¹³¹I uptake.