Patients with low risk differentiation thyroid cancer (DTC) undergoing thyroidectomy show no improved outcomes with the use of postoperative radioactive iodine ablation compared to those who do not receive this therapy, suggesting that these patients may be spared the previously common treatment.
The take-home message of the study for clinicians should be “to discontinue routine administration of radioactive iodine ablation in patients with low-risk thyroid cancer,” the author said. Principal Sophie Leboulleux, MD, PhD. Medscape Medical News.
The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Lebouleux, of the Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.
While the American Thyroid Association (ATA) guidelines already indicate that radioactive iodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the recommendation is only a “weak recommendation”, supported by “low quality evidence”.
However, the new findings should give this level of evidence a much-needed boost, an expert said. “I think the main contribution of this article is to change the level of evidence to ‘high quality’, thus making the recommendation ‘strong’ rather than ‘weak,'” said David S. Cooper, MD. Medscape Medical News.
Cooper, a professor of medicine and radiology at Johns Hopkins University School of Medicine, in Baltimore, Maryland, also wrote a editorial which accompanies Leboulleux’s study.
The ability to safely spare patients the radioactive iodine ablation step after thyroidectomy also has significant cost and convenience advantages, Cooper pointed out.
The new results come from the prospective, randomized, phase 3 Trial Stimulation Ablation 2 (ESTIMABL2), in which 730 patients from 35 centers in France with low-risk DTP undergoing thyroidectomy were recruited between May 2013 and March 2017.
Patients were randomized to receive either postoperative radioactive iodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioactive iodine (n = 367).
The patients had an average age of 52 years and 83% were women. Approximately 96% had papillary tumors, and the pathological tumor node (pTN) stages were mainly thyroid pT1b with node status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioactive iodine ablation have yielded inconsistent results, note Leboulleux and colleagues. Hence their decision to look at this prospectively.
Results were based on the groups’ event rates, defined as the presence of abnormal foci of radioactive iodine uptake on whole body examination requiring treatment (in the radioactive iodine only group), abnormal ultrasound findings of the neck or increased levels of radioactive iodine. thyroglobulin or anti-thyroglobulin antibodies.
After a 3-year follow-up, event-free rates in both groups were very high – and almost identical – at 95.6% among those who did not receive radioactive iodine ablation and 95.9% in the radioactive iodine group, for a difference between the groups of –0.3 percentage points, which met the non-inferiority criteria for the group without radioactive iodine.
Similarly, the events that occurred were also roughly equally distributed between the group without radioactive iodine (16 events, 4.4%) and the group with radioactive iodine (15 events, 4.1%).
Of the patients who had events, subsequent treatments, including surgery, administration of radioactive iodine, or both, were required for four patients in the no radioactive iodine group and 10 in the iodine group radioactive, and additional treatments were not required for the other patients who experienced events.
There were no differences between those who underwent and those who did not underwent events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant difference between the groups.
Of the adverse events that occurred in 30 patients, none were determined to be treatment-related and there were no thyroid-related deaths.
The recurrence rates match the rates seen overall with low-risk thyroid cancer, the authors note.
“We observed that less than 5% of patients in both groups had events that included abnormal findings on whole body ultrasound or neck ultrasound or elevated levels of thyroglobulin or anti-thyroglobulin antibodies in the during the first 3 years of follow-up,” they report. .
“This rate is consistent with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not increased in the absence of postoperative radioactive iodine administration.”
Costs saved to patients, lost work
Cooper explained the benefits for patients of avoiding radioactive iodine ablation.
For one thing, the recombinant human TSH needed to prepare for radioactive iodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having to co-pay, he explained. .
“Additionally, patients typically have to take time off work, which is also an expense to society and to them if they don’t get paid for the days they don’t work,” Cooper added.
A possible limitation of the study is whether 3 years is a sufficient follow-up period to detect events. However, Cooper said he considered the period to be sufficient.
“As the authors point out, most thyroid cancer recurrences are detected within the first 3-5 years of initial treatment, so…the 3-year window is still clinically relevant,” he said. -he declares.
Regarding the study including only centers in France, Cooper adds: “I don’t think this is a limitation of the study. risk papillary thyroid cancer.”
Some continue to use radioactive iodine, but lobectomies add to decline
Despite mounting evidence of the lack of benefit of radioactive iodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTP until relatively recently.
“[While] US guidelines changed in 2015 in favor of no radioactive iodine in patients with low-risk differentiated thyroid cancer, this study should help change European guidelines,” Leboulleux said. results will help change practices in the United States and Europe.”
In addition to awareness of guidelines and new evidence, another reason for the decline of radioactive iodine ablation for low-risk DTPs is the increasing use of thyroid lobectomy, which does not involve the use radioactive iodine ablation, rather than total thyroidectomy, Cooper noted.
“The [new] NEJM will hopefully further reduce the inappropriate use of radioactive iodine in low-risk patients,” he concluded.
The study received support from Ministry of Health thanks to a grant from the National Cancer Institute. Authors did not report any relevant financial relationships.