Identifying Radioiodine-Refractory Disease and Progression Beyond Local Therapy

In this segment, Dr. Greg Randolph discusses how the treatment landscape evolves when differentiated thyroid cancer (DTC) progresses beyond traditional local therapies such as surgery and radioactive iodine. He highlights the growing role of neoadjuvant systemic therapy for patients presenting with significant visceral invasion, cases where tumors abut or invade critical structures like the larynx, trachea, esophagus, great vessels, muscle, or nerves (“R1/R2 interfaces”).

Rather than proceeding directly to extensive surgery, clinicians are increasingly using next-generation sequencing (NGS) to identify actionable molecular alterations. Targeted agents (e.g., RET inhibitors such as selpercatinib for RET-altered tumors, or other fusion-directed therapies) can be used preoperatively to shrink tumors and potentially improve surgical margins. When no targetable mutation is found, broader tyrosine kinase inhibitors such as lenvatinib may be employed in the neoadjuvant setting. Early data suggest this approach can reduce tumor burden, enable less morbid surgery, and reshape management of advanced DTC.