In the French phase III ESTIMABL2 trial reported in The New England Journal of Medicine, Leboulleux et al found that no use of radioiodine was noninferior to radioiodine ablation in the occurrence of functional, structural, or biologic events among patients undergoing thyroidectomy for low-risk differentiated thyroid cancer.
Study Details
In the multicenter trial, 730 patients who were evaluable at 3 years (out of 776 enrolled) were randomly assigned between May 2013 and March 2017 to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).
The primary outcome measure was 3-year rate of a composite endpoint of functional, structural, and biologic events, including presence of abnormal foci of radioiodine uptake on whole-body scanning requiring subsequent treatment (radioiodine group only), abnormal findings on neck ultrasonography, and elevated levels of thyroglobulin or thyroglobulin antibodies. Noninferiority was defined as a between-group difference of < 5% in event rate.
In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years.— Leboulleux et al
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Key Findings
At 3 years, the proportion of patients without an event was 95.6% (95% confidence interval [CI] = 93.0%–97.5%) in the no-radioiodine group vs 95.9% (95% CI = 93.3%–97.7%) in the radioiodine group (difference = −0.3%, 90% CI = −2.7% to 2.2, meeting noninferiority criterion).
In the radioiodine group, events consisted of abnormal foci of radioiodine uptake in two patients, abnormal lymph node in two, elevated thyroglobulin level after recombinant human thyrotropin in nine, and elevated thyroglobulin antibodies in two. In the no-radioiodine group, events consisted of abnormal lymph node in three patients, elevated thyroglobulin level during thyroid hormone treatment in seven, and elevated thyroglobulin antibodies in seven.
A nested case: control analysis of 90 evaluable patient samples showed similar overall molecular alterations in patients with vs without an event; a small difference in BRAF alterations was observed (61% v 53%).
No treatment-related adverse events were reported.
The investigators concluded, “In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years.”
Sophie Leboulleux, MD, PhD, of Gustave Roussy, Universite Paris Saclay, Villejuif, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the French National Cancer Institute. For full disclosures of the study authors, visit nejm.org.
