Background ESTIMABL2, a multicentre randomised phase 3 trial in patients with low-risk differentiated thyroid cancer (ie, pT1am or pT1b, N0 [no evidence of regional nodal involvement] or Nx [involvement of regional lymph nodes that cannot be assessed in the absence of neck dissection]), showed the non-inferiority of a follow-up strategy without radioactive iodine (¹³¹I) administration compared with a postoperative ¹³¹I administration at 3 years post-randomisation. Here, we report a pre-specified analysis after 5 years of follow-up.

Methods Patients treated with total thyroidectomy with or without prophylactic neck lymph node dissection, without postoperative suspicious findings on neck ultrasonography, were randomly assigned to the no-radioiodine group or to the radioiodine group (1•1 GBq-30 mCi after recombinant human thyrotropin-stimulating hormone). Follow-up consisted of annual thyroglobulin and thyroglobulin antibody determinations during levothyroxine treatment and neck ultrasonography in odd-numbered years. An event was defined as abnormal foci of ¹³¹I uptake on the post-treatment whole-body-scan requiring subsequent treatment, abnormal neck ultrasonography, elevated thyroglobulin levels, increasing titres or appearance of thyroglobulin antibody (using the same laboratory assay), or a combination of these definitions. Non-inferiority of the proportion of patients without an event in one group compared with the other at 5 years after randomisation was shown if this proportion and its CI did not differ by more than -5%. This study was registered on ClinicalTrials.gov (NCT01837745) and is completed.

Of the 776 patients (n=642 [82•7%] female and n=134 [17•3%] male, median age 52•9 years [IQR 42•6-63•1]) enrolled, 698 were evaluable at 5 years. The proportions of patients without events were 93•2% in the no-radioiodine group and 94•8% in the radioiodine group, for a difference of -1•6% (90% CI -4•5 to 1•4). Events consisted of structural or functional abnormalities (n=11) and biological abnormalities (n=31).

Interpretation The non-inferiority of a follow-up strategy compared with postoperative ¹³¹I administration in low risk differentiated thyroid cancer was confirmed at 5 years. There is no loss of opportunity in following these patients without postoperative ablation.

Funding Programme de Recherche Hospitalier Clinique.