Postoperative radioiodine is unnecessary for patients with low-risk differentiated thyroid cancer who have undergone thyroidectomy, a large UK randomised trial shows, potentially saving thousands of patients from undergoing the treatment.
Thyroid cancer is the seventh most common type of cancer globally, with 821,000 new cases diagnosed each year and approximately 48,000 annual deaths, as of 2022.
It has been standard practice internationally to perform a total thyroidectomy on patients with well differentiated thyroid cancer followed by postoperative radioiodine, also known as radioiodine ablation.
However, radioiodine ablation involves hospital admission and isolation, together with the possibility of treatment-related side effects, as well as the need to avoid close contact with children for several days once discharged.
Writing in The Lancet, the researchers noted controversy over this practice, pointing to previous observational studies and one randomised trial called ESTIMABL2 indicating that selected patients with low-risk differentiated thyroid cancer could avoid ablation.
As such, their recent Iodine or Not (IoN) study was a multicentre, Cancer Research UK-funded, phase three trial designed to assess whether recurrence-free survival was non-inferior after no ablation in selected low-risk thyroid cancer patients.
Recurrence-free rates without radioiodine ablation
The researchers recruited 504 patients (77% female) aged 17-80 years who had complete (R0) resection following total thyroidectomy; stage pT1, pT2, pT3 or pT3a disease; and N0, Nx or N1a disease.
All patients who had a thyroidectomy were randomly assigned 1:1 to have either no ablation or 1.1 GBq ablation, with a median 6.6 years follow-up in the ablation group and a median 6.8 years follow-up in the no ablation group.
The researchers observed patients with annual neck ultrasound and six-monthly serum thyroglobulin measurements.
They found five-year recurrence-free rates were 97.9% in the no ablation group compared with 96.3% in the ablation group in an intention-to-treat analysis.
The five-year absolute risk difference was 0.5 percentage points, they reported, showing non-inferiority was reached.
There were no treatment-related deaths and adverse events were similar between groups, with the most common being fatigue, lethargy and dry mouth.
‘The IoN trial shows that ablation (or postoperative radioiodine) can be avoided for patients with pT1, pT2, and N0 or Nx tumours with no adverse features,’ the researchers concluded.
There were only a small number of patients with pT3, pT3a, or N1a tumours in the IoN trial, meaning subgroup analyses were underpowered for these patients and care was need when applying the results of the trial to all pT3 or N1a tumours, they cautioned.
‘A clinical decision was made to not provide a definitive statement on the basis of numerically higher recurrence rates in these patients, even though the rates were not higher among patients who did not have postoperative radioiodine than those who did have ablation,’ the researchers wrote.
Change in UK policy required
The results from IoN, taken with the findings from ESTIMABL2, suggested that at least 400,000 patients with low-risk differentiated thyroid cancer worldwide could avoid radioiodine ablation after a total thyroidectomy.
‘A change in UK policy to not offer ablation to all patients with suitably low-risk disease could mean that approximately 2,500 patients could safely avoid ablation each year (if 70% of patients newly diagnosed with differentiated thyroid cancer would typically be given ablation),’ the researchers said.
Professor Allan Hackshaw, a trial investigator from UCL Cancer Institute in London, said the results showed radioactive iodine represented over-treatment in these low-risk patients.
‘The only impact of not receiving this radiotherapy was a positive one on people’s quality of life,’ he said.
This was particularly important because around a third of patients in the study were aged 40 years or younger, and many would have children to care for, Professor Hackshaw noted.
‘Being spared radioactive iodine therapy means they will be able to get back to a near normal life much more quickly, as well as receiving the emotional and physical support of their families in the weeks after their operation,’ he added.
In 2020,
