In a UK phase III trial (IoN) reported in The Lancet, Mallick et al compared survival outcomes among patients with low-risk differentiated thyroid cancer who underwent thyroidectomy with no postoperative radioiodine ablation vs thyroidectomy plus ablation.
Study Details
In the multicenter noninferiority trial, 504 patients (intent-to-treat [ITT] population) undergoing thyroidectomy were randomly assigned between June 2012 and March 2020 to receive no ablation (n = 251) or ablation (n = 253). In the per-protocol population, 249 patients in the no-ablation group did not have ablation and 231 in the ablation group had ablation. Eligible patients had: complete (R0) resection following total thyroidectomy; stage pT1, pT2, pT3 (according to TNM version 7 staging) or pT3a (according to TNM version 8 staging) disease; and N0, Nx, or N1a disease. The primary endpoint of the trial was 5-year recurrence-free survival in the ITT population, with a noninferiority margin of 5 percentage points.
Key Findings
Median follow-up was 6.8 years (interquartile range [IQR] = 5.6–8.6 years) in the no-ablation group and 6.6 years (IQR = 4.8–8.5 years) in the ablation group.
Recurrence-free survival rates at 5 years were 97.9% (95% confidence interval [CI] = 96.1%–99.7%) in the no-ablation group vs 96.3% (95% CI = 93.9%–98.7%) in the ablation group in the ITT population; the 5-year absolute risk difference was 0.5 percentage points (95% CI = –2.2 to 3.2 percentage points, P for noninferiority = .033), with noninferiority of the no-ablation group being achieved. In the per-protocol population, 5-year recurrence-free survival was 97.9% (95% CI = 96.1%–99.7%) vs 96.9% (95% CI = 94.7%–99.1%).
Overall, recurrence rates were higher among patients with pT3 or pT3a tumors vs pT1 or pT2 tumors (4 [9%] of 46 vs 13 [3%] of 458) and among patients with N1a vs N0 or Nx tumors (6 [13%] of 47 patients vs 11 [2%] of 457); however, rates in these groups were similar among patients in the no-ablation group.
In the per-protocol population, adverse events of any grade were similar in the no-ablation group vs the ablation group; the most common were fatigue (25% vs 28%), lethargy (14% vs 14%), and dry mouth (10% vs 9%). Grade 3 adverse events occurred in four patients (2%) in the no-ablation group and one patient (<1%) in the ablation group. No grade 4 adverse events or treatment-related deaths were observed.
The investigators concluded: “The IoN trial shows that ablation (or postoperative radioiodine) can be avoided for patients with pT1, pT2, and N0 or Nx tumors with no adverse features. Many patients with low-risk differentiated thyroid cancer worldwide can safely avoid postoperative radioiodine and its related hospitalization and side effects, which in turn results in lower health-care costs.”
Allan Hackshaw, MSc, of Cancer Research UK & UCL Cancer Trials Centre, UCL Cancer Institute, London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Cancer Research UK. For full disclosures of all study authors, visit thelancet.com.
