Avoiding Radioiodine Therapy following Thyroidectomy in Patients with Low-Risk Thyroid Cancer

SUMMARY: The American Cancer Society estimates that about 43,800 new cases of thyroid cancer will be diagnosed in the United States in 2022 and about 2,230 patients will die of the disease. Differentiated Thyroid Cancer (DTC) is the most common endocrine malignancy and includes Papillary, Follicular, and Hürthle-cell cancers, with Papillary thyroid cancers accounting for 80% of them. Majority of patients with DTC have clinical Stage I or Stage II disease, with a recurrence rate of less than 5% and cancer-related death rates even lower. Risk factors for recurrence include tumor size, multifocality, capsular or angioinvasion, degree of cervical lymph node involvement, existence of BRAF V600E Mutation, and thyroglobulin levels more than 0.5 ng/mL, after thyroidectomy.

Even though Radioiodine (iodine-131) therapy is not recommended for patients with a unifocal microcarcinoma (10 mm or less in diameter) following thyroidectomy, Radioiodine therapy is generally offered to a majority of patients with low-risk thyroid cancer, both to ablate residual normal thyroid tissue and to treat unresectable persistent disease. The benefits of this intervention however remain controversial. .

The authors conducted a prospective, multicenter, randomized, Phase III Essai Stimulation Ablation 2 (ESTIMABL2) trial involving patients with low-risk thyroid cancer, to assess the non-inferiority of observation versus postoperative Radioiodine therapy, following thyroidectomy. In this study, a total of 776 patients with low-risk Differentiated Thyroid Cancer who were undergoing thyroidectomy were randomly assigned 1:1 to receive ablation with postoperative Radioiodine therapy at a dose of 1.1 GBq (N=389) or no Radioiodine therapy (N=387). Enrolled patients had Differentiated Thyroid Carcinoma (Papillary, Follicular, or Oncocytic/Hürthle-cell cancer), with a multifocal pT1a tumor or a pT1b tumor. None of the patients had regional lymph node involvement, extrathyroidal extension or aggressive histologic subtypes (tall-cell, clear-cell, columnar-cell, and diffuse sclerosing variants of Papillary thyroid cancer, poorly differentiated). The mean patient age was 52 years, and 83% were women, 96% had papillary tumors 81% had pT1b N0 or Nx disease. All patients had normal results on postoperative neck ultrasonography. The follow-up protocol consisted of the measurement of thyroglobulin and thyroglobulin antibodies in all patients at 10 months and yearly thereafter. Ultrasonography of the neck was performed in all patients 10 months and 3 years after randomization. Disease-related events included residual or recurrent disease on neck ultrasonography and a serum thyroglobulin level of more than 1 ng/mL in the group receiving radioiodine and a level of more than 5 ng/mL in the nontreated group. No diagnostic Radioiodine scanning was performed after the whole-body scanning that was performed after therapy. The Primary objective was to assess whether no Radioiodine therapy was noninferior to Radioiodine therapy, with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities, indicating residual or recurrent disease at 3 years.

After 3 years of follow up, there were no clinically meaningful differences in any of the end points between the two groups and the percentage of patients without an event was 95.6% in the no-Radioiodine therapy group and 95.9% in the Radioiodine therapy group, a result that met the noninferiority criteria. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng/mL during thyroid hormone treatment. BRAF V600E molecular alterations, which are associated aggressive tumor characteristics, were found in approximately 50% of the samples in each treatment group. The mutational status did not influence event rates in these low-risk patients. No treatment-related adverse events were reported and there was no difference in Quality-of-Life scores between the two groups.

It was concluded that in patients with low-risk thyroid cancer undergoing thyroidectomy, follow up without the use of Radioiodine therapy was noninferior to an ablation strategy with Radioiodine therapy, suggesting that patients with low-risk disease generally do well regardless of whether they receive Radioiodine therapy.

Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer. Leboulleux S, Bournaud C, Chougnet CN, et al. N Engl J Med 2022; 386:923-932