Summary: In selected patients with low-risk differentiated thyroid cancer after complete total thyroidectomy, omission of postoperative radioiodine was non-inferior to 1.1 GBq ablation for 5-year recurrence-free survival. The finding most directly supports patients with pT1-pT2, N0 or Nx disease and no adverse features.
PICO Summary
| Element | Detail |
|---|---|
| Population | 504 patients after complete total thyroidectomy for low-risk differentiated thyroid cancer at 33 UK centres; phase 3 non-inferiority RCT with median follow-up about 6.7 years. |
| Intervention | No postoperative radioiodine ablation (n=251 intention-to-treat). |
| Comparison | Postoperative radioiodine ablation with 1.1 GBq (n=253 intention-to-treat). |
| Outcome | Five-year recurrence-free survival was 97.9% without ablation versus 96.3% with ablation. Absolute risk difference 0.5 percentage points (95% CI -2.2 to 3.2); non-inferiority P=0.033. Seventeen recurrences occurred overall. |
No Radioiodine After Thyroidectomy (IoN)
Phase 3 non-inferiority RCT - low-risk DTC - 5 years
Omitting postoperative radioiodine was non-inferior for 5-year recurrence-free survival in selected low-risk differentiated thyroid cancer after complete thyroidectomy.
Expert Commentary
IoN is an important de-escalation trial because it tests whether a familiar treatment can be safely omitted rather than adding another therapy. In carefully selected patients after complete total thyroidectomy, five-year recurrence-free survival without radioiodine was extremely high and met the prespecified non-inferiority criterion. The result aligns with a risk-adapted approach and can spare hospitalization, radiation precautions, salivary adverse effects, and cost. Selection is the essential caveat. Recurrence was more frequent among participants with pT3 or pT3a and N1a disease, and the investigators' interpretation most clearly supports pT1-pT2, N0 or Nx tumours without adverse features. The trial was open label, event numbers were low, and follow-up should continue because differentiated thyroid cancer can recur late. Can I use this with my patients? Yes, when discussing postoperative management with adults who match the low-risk profile, have had complete resection, and can participate in reliable thyroglobulin and ultrasound surveillance. This result should not be generalized to incomplete resection, aggressive histology, adverse molecular or pathological features, substantial nodal disease, or distant metastasis. Shared decision-making should document both the low absolute recurrence risk and the surveillance plan. The next step is longer follow-up and better definition of the smaller higher-risk subgroups represented in the trial.
References
Mallick U, Newbold K, Beasley M, et al. Thyroidectomy with or without postoperative radioiodine for patients with low-risk differentiated thyroid cancer in the UK (IoN): a randomised, multicentre, non-inferiority trial. Lancet. 2025;406(10498):52-62. doi:10.1016/S0140-6736(25)00629-4. PMID: 40543520.