BACKGROUND
The majority of patients with thyroid cancer do very well with an excellent prognosis. This is because we have very effective treatments, including surgery to remove the cancer and radioactive iodine therapy to destroy any remaining thyroid cancer after surgery. However, 5 to 15% of patients have more advanced cancer which can develop resistance to radioactive iodine therapy (radioactive iodine–refractory, RAIR), which is linked to markedly worse clinical outcomes. In this case, the next step has traditionally been to begin systemic therapy (chemotherapy) with drugs known as tyrosine-kinase inhibitors (TKIs). However, TKIs, while helpful, do not cure the cancer and >90% of patients experience at least one adverse event during therapy. Further, many patients have no symptoms from their cancer and may ultimately experience worse quality of life from treatment than from the disease itself. This has led to a shift by the ATA 2025 guidelines in recommending local treatment first before starting systemic therapy.

THE FULL ARTICLE TITLE
Ringel MD et al. 2025 American Thyroid Association management guidelines for adult patients with differentiated thyroid cancer. Thyroid 2025;35(8):841-985.

SUMMARY OF THE STUDY
The 2025 ATA thyroid cancer guidelines refer to patients with differentiated thyroid cancer, almost all of which are papillary thyroid carcinoma.

The rationale for prioritizing localized therapy before—or sometimes instead of—systemic therapy in metastatic radioactive iodine–refractory thyroid cancer has become increasingly clear in recent years and is now strongly reflected in both the 2025 American Thyroid Association (ATA) and the current National Comprehensive Cancer Network (NCCN) guidelines.

This is because of several factors: 1) RAIR thyroid cancer does not uniformly result in rapid progression of the cancer, 2) TKIs, while helpful, do not cure the cancer and >90% of patients experience at least one adverse event during therapy, 3) many patients have no symptoms from their cancer may ultimately experience worse quality of life from treatment than from the disease itself, 4) local therapies have the potential to provide control of the cancer, 5) local treatment may help prolong TKI effectiveness, and 6) the importance of maintaining long-term quality of life in patients who often live many years with metastatic thyroid cancer.

Local therapies may include 1) active surveillance with serial imaging at intervals of 3 to 12 months, 2) repeat surgery, 3) targeted radiation therapy and 4) radiofrequency ablation (RFA). The ATA recommendations strongly support local therapy for symptomatic metastatic disease. Local, directed therapy can rapidly improve symptoms, prevent complications, and improve functional outcomes.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Given that many RAIR thyroid cancers are not rapidly progressing, and that TKIs are effective but far from benign in their side effects, well selected local therapies can often control disease for prolonged periods (“systemic therapy–free survival”) while allowing patients to maintain a better quality of life. The expanding role of surgery, directed radiation therapy and RFA is not about replacing systemic therapy altogether, but about using the right treatment at the right moment—and sometimes buying patients years before they truly need long-term systemic treatment. Indeed, systemic therapy should be reserved for patients with progressive, symptomatic cancer that fails to respond to radioactive iodine therapy and cannot be surgically removed. Systemic therapy is typically started when cancer growth exceeds 20% over 12 to 14 months.

As always, these decisions should result from a shared-decision making discussion with the patient and their doctor.

— Alan P. Farwell, MD

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