2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer

Key guideline recommendations

1. Recommendation 11: a) Active surveillance can be offered as an appropriate management option to selected patients with cT1aN0M0 papillary thyroid carcinoma. Shared clinical decision-making between the patient and care team about the risks and benefits of this approach is essential. b) Ultrasound-guided percutaneous ablation can be considered in selected patients as an alternative to active surveillance or surgery for cT1aN0M0 papillary carcinoma; shared decision-making about its risks and benefits is essential.

   Conditional recommendation, Low certainty evidence – for both

2. Recommendation 14: In patients under active surveillance, surgery is indicated in these situations: evidence of new biopsy-proven lymph node metastasis, growth of the primary tumour by 3 mm or more, distant metastasis, evidence of extrathyroidal extension, posterior growth, and also in case of patient anxiety, inability to follow up and/or patient preference for surgery.

   Good Practice Statement

3. Recommendation 15 (extent of surgery): a) When surgery is performed for thyroid cancer 2 cm or smaller without gross extrathyroidal extension (cT1) and without metastases (cN0M0), the initial surgery should be thyroid lobectomy, unless there is bilateral cancer or another indication to remove the contralateral lobe. b) In patients with low-risk unilateral cancer larger than 2 cm and up to 4 cm (cT2N0M0), lobectomy may be the preferred initial surgery because of its substantially lower risk and morbidity; however, the patient and care team may choose total thyroidectomy, based on disease characteristics, suspicious nodules in the contralateral lobe and/or patient preference, to allow radioactive iodine therapy and/or facilitate follow-up. If lobectomy is performed, the patient should be counselled about the possibility of conversion to total thyroidectomy or the need for completion surgery if high-risk features become apparent during or after surgery. c) In cancer larger than 4 cm (cT3a), cancer of any size with gross extrathyroidal extension (cT3b or cT4), or clinically apparent metastasis to lymph nodes (cN1) or distant sites (cM1), the initial surgery should include total thyroidectomy with removal of all visible primary tumour and lymph node dissection, unless contraindicated.

   15a and 15c: Strong recommendation, Moderate certainty evidence

4. Recommendation 28a: The ATA 2025 risk stratification system, which assesses tumour pathology features and the number of involved cervical lymph nodes together with the AJCC staging system, postoperative imaging and serum thyroglobulin and anti-thyroglobulin antibody testing (as needed), is recommended for determining the risk of persistent or recurrent structural disease (locoregional and/or distant) and/or survival in patients with differentiated thyroid cancer.

   Strong recommendation, Moderate certainty evidence

5. Recommendation 32 (radioactive iodine after thyroidectomy): a) Remnant ablation after total thyroidectomy is not routinely recommended in patients with ATA low-risk differentiated thyroid cancer. b) Adjuvant radioactive iodine therapy after total thyroidectomy may be considered in patients at ATA low-intermediate and intermediate-high risk of recurrence. c) Adjuvant radioactive iodine therapy after total thyroidectomy is routinely recommended in ATA high-risk patients. d) In patients with distant metastases at initial diagnosis of differentiated thyroid cancer, radioactive iodine therapy after total thyroidectomy is routinely recommended.

   32a: Strong, High certainty; 32b: Conditional recommendation, Low certainty

6. Recommendation 34a: In patients with differentiated thyroid cancer for whom remnant ablation or adjuvant radioactive iodine therapy is planned, preparation with recombinant human TSH (rhTSH) stimulation is preferred over thyroid hormone withdrawal.

   Strong recommendation, High certainty evidence

7. Recommendation 46a: Long-term TSH suppression is not suggested for patients with low-‎ or intermediate-risk disease who have no evidence of biochemical or structural recurrence. (46b: The risks and benefits of TSH suppression and TSH targets should be reassessed over time — Good Practice Statement.)

   Conditional recommendation, Low certainty evidence

8. Recommendation 61: In radioactive iodine-refractory differentiated thyroid cancer, biomarker testing of tumour tissue to identify actionable oncogenic driver alterations should be performed before starting systemic therapy for progressive disease.

   Strong recommendation, Moderate certainty evidence

9. Recommendation 62: For patients with progressive radioactive iodine-refractory differentiated thyroid cancer who have no FDA-approved first-line therapy linked to an actionable biomarker, treatment with a multikinase inhibitor, lenvatinib or sorafenib, is recommended. In most cases, lenvatinib is the preferred first-line multikinase inhibitor.

   Strong recommendation, High certainty evidence

Study population

Clinical significance and place in guidelines

Limitations