medwireNews: Among patients with low-risk differentiated thyroid cancer participating in the IoN trial, the 5-year recurrence-free survival (RFS) was noninferior for those who did not receive radioactive iodine after total thyroidectomy versus those who did.
These findings are similar to those from the primary analysis and 5-year follow-up of the ESTIMABL2 trial, say the investigators in The Lancet, noting that the two trials “were designed at a similar time and to be complementary.”
They highlight, however, that “[t]he IoN trial provides data on a wider group of patients than ESTIMABL2.”
The researchers therefore write: “Many patients with low-risk differentiated thyroid cancer worldwide can safely avoid postoperative radioiodine and its related hospitalisation and side-effects, which in turn results in lower health-care costs.”
The phase 3 study was conducted at 33 UK cancer centers and enrolled 504 patients who had a total thyroidectomy with an R0 resection. They had to have tumors of stage pT1, pT2, pT3 (according to Tumor, Node, Metastasis [TNM] staging version 7), or pT3a (according to TNM8) disease, and N0, Nx, or N1a disease.
In the intention-to-treat population, at a median follow-up of 6.7 years, eight recurrences occurred among the 251 patients who were randomly assigned to no postoperative radioiodine (also called ablation) and nine among their 253 counterparts allocated to receive 1.1 GBq of radioiodine.
The corresponding 5-year RFS rates were 97.9% and 96.3%, equating to an absolute risk difference of 0.5 percentage points and a nonsignificant hazard ratio (HR) of 0.84.
Similarly, in the per-protocol analysis – which included 249 patients in the no radioiodine group and 231 in the radioiodine group – the 5-year RFS rates were 97.9% and 96.9%, respectively. The absolute risk difference was –0.1 percentage points and the HR was a nonsignificant 1.03.
“The point estimates and [confidence intervals] are within the 5-percentage point non-inferiority margin,” demonstrating the noninferiority of omitting radioiodine, write Allan Hackshaw (UCL Cancer Institute, London, UK) and co-researchers.
They point out that the recurrence rate was higher among patients with pT3 or pT3a tumors than those with pT1 or pT2 tumors, but this was the case regardless of the treatment group. For instance, in the per-protocol population, the recurrence rates were 8.7% versus 5.3% among participants who omitted radioiodine and 9.1% versus 4.7% among those who received it.
The observations were similar for N1a versus N0 or Nx tumors, with higher rates in the former group but no additional increase in the no radioiodine group (per-protocol population: 9.1 vs 2.6%) compared with the radioiodine group (18.2 vs 1.4%).
Adverse events occurred at comparable rates in the no radioiodine and radioiodine arms, with the most common all-grade events being fatigue (25 vs 28%), lethargy (14 vs 14%), and dry mouth (10 vs 9%). Moreover, there were no treatment-related deaths in either group.
Summarizing the results, Hackshaw and colleagues say that together the IoN and ESTIMABL2 trials “provide level 1 evidence that convincingly shows that patients with pT1 tumours and no adverse features can avoid ablation (postoperative radioiodine), as this does not affect their risk of recurrence.”
They continue: “IoN now adds to this evidence and indicates that pT2 tumours with no adverse features also do not need ablation. Evidence either for or against the need for ablation in pT3 or pT3a […] or N1a tumours is insufficient.”
The author of an accompanying comment says that “[t]he IoN study provides more high-level, practice-changing evidence that enables us to decrease the extent of treatment for patients with low-risk thyroid cancer,” describing the trial as “an important stepping stone on our path to better individualising therapy.”
Dana Hartl, from Gustave Roussy in Villejuif, France, remarks that “[t]he next step will be to assess whether ablation modifies outcomes in patients with intermediate-risk thyroid cancer.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature
Lancet 2025; doi:10.1016/S0140-6736(25)00629-4
Lancet 2025; doi:10.1016/S0140-6736(25)00781-0
