Is Radioiodine Beneficial After Thyroidectomy?

Patients with low-risk differentiated thyroid cancer show similar outcomes after 5 years regardless of whether they received radioactive iodine following total thyroidectomy, results from a randomized trial show, suggesting patients can be safely spared the additional radioiodine treatment, with some exceptions, including high-risk cases.

“This is the first randomized, prospective trial showing that radioiodine is useless in low-risk thyroid cancer,” first author Sophie Leboulleux, MD, PhD, of the Department of Endocrinology and Diabetology, Geneva University Hospitals, Geneva, Switzerland, told Medscape Medical News.

“The longer follow-up should convince clinicians not to give iodine,” she said of the study, published in The Lancet Diabetes & Endocrinology.

Radioiodine has long been part of the standard of care in treating thyroid cancer; however, in recent years, the consensus has been to avoid the therapy in patients with low-risk follicular cell–derived thyroid cancer with stage I disease, involving unifocal microcarcinomas that are 10 mm in diameter or smaller.

In terms of other low-risk thyroid cancers, however, the evidence regarding the benefits of radioiodine has not been conclusive, with one meta-analysis showing inconsistent benefit, while another review showed no benefit.

To investigate, Leboulleux and her colleagues conducted the multicenter, phase 3 ESTIMABLE2 trial, involving 776 patients in France with thyroid cancer who received a total thyroidectomy between May 2013 and March 2017 and had a low risk for recurrence, with no postoperative suspicious findings on neck ultrasound.

The patients were randomized to receive either no radioiodine or radioiodine (1.1 GBq [30 mCi] of iodine-131 after recombinant human thyrotropin–stimulating hormone), following the thyroidectomy.

At 3 years following randomization, the original study showed that outcomes with the postoperative strategy of no radioiodine were not inferior to radioiodine use in relation to the occurrence of functional, structural, and biologic events, with the proportion of patients having no events being even slightly lower in the group that did not vs did receive radioiodine (95.6% vs 95.9%, respectively).

However, with most recurrences of thyroid cancer known to occur in the postoperative period extending to 5 years, the study’s 3-year follow-up was determined to possibly be too short, particularly considering the indolent nature of most low-risk and intermediate-risk thyroid cancers.

To further investigate patient outcomes at 5 years, the authors conducted the current follow-up analysis.

Like the original study, non-inferiority was defined as having a less than 5% difference between the two groups in terms of proportion of patients having events occurring over the study period.

Events were defined as either the development of abnormal foci of radioiodine uptake on posttreatment whole-body scan requiring treatment; abnormal neck ultrasonography; elevated thyroglobulin levels, increasing titers; the appearance of thyroglobulin antibody; or a combination of these definitions.

Of 698 patients from the study who were evaluable at 5 years, the results showed the proportion of patients who did not have events was again slightly lower among those who did not receive radioiodine, at 93.2%, vs those who did, at 94.8%, for a difference of −1.6%.

Key factors associated with the development of an event included having a postoperative serum thyroglobulin level > 1 ng/mL, being between 55 and 60 years old, having a follicular histology, and having a larger tumor size.

Biologic events were the most common, accounting for 74% of events, while biologic, functional, and structural events occurred in similar numbers in both groups over the follow-up period. The rate of incomplete structural responses was low and also occurred in similar proportions in both groups.

Of patients who had recurrences, thyroglobulin levels at the time of structural recurrence ranged from 0.1 to 3.0 ng/mL in patients in the no-radioiodine group and between

Among 19 patients with elevated thyroglobulin levels, including 9 in the radioiodine group and 10 in the no-radioiodine group, 10 received subsequent treatment; however, among the untreated patients, 6 (67%) of 9 had spontaneous normalization of serum thyroglobulin levels.

“This emphasizes the fact that when thyroglobulin levels are slightly elevated, there is no emergency to administer empiric activities of radioiodine,” the authors explained.

In terms of prognostic factors, they added that if postoperative thyroglobulin level is considered as a parameter to decide for radioiodine administration, “the number of patients to be treated will decrease drastically.”

Importantly, while a thyroglobulin level > 1 ng/mL was found to be a prognostic factor for an event in the present study, the threshold of 2 ng/mL was used to monitor the patients without radioiodine to define an event; therefore, “a cutoff of 2 ng/mL could be used as a threshold to give radioiodine to these patients,” the authors noted.

Ultimately, however, “proof that the outcome of these patients will be improved by radioiodine is still needed with prospective studies,” they concluded.

While research shows the majority of follicular cell–derived thyroid cancer recurrences are detected within the first 5 years of follow-up, “late recurrences can occur, and the patients from the present study are scheduled for further follow-up,” they added.

Leboulleux reported receiving consultancy fees from Eisai, Eli Lilly and Company, and Bayer.