Guidelines on the Use of Radioactive Iodine in Low-Risk Thyroid Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • American Thyroid Association (ATA) Low-Risk of Recurrence Overview:
    • Patients considered low-risk (pre- or post-operative):
      • Intrathyroidal papillary thyroid cancer ≤ 4 cm:
        • T1 to T2
      • No clinical nodal involvement:
        • N0 or minimal N1a
      • No distant metastasis (M0)
      • No aggressive histologic variants
      • No gross extrathyroidal extension
  • Core Randomized Trials:
    • ESTIMABL1 (2012, France):
      • Design:
        • 2 × 2 factorial randomized control trial (RCT):
          • Comparing low-dose (1.1 GBq) vs high-dose (3.7 GBq) radioactive iodine (RAI), and rhTSH stimulation vs thyroid hormone withdrawal for remnant ablation
      • Primary Outcome:
        • Remnant ablation success at 6 to 10 months:
          • ~92% to 95%
        • 5‑Year Follow-Up (2018):
          • 98% no evidence of disease
          • No differences between RAI dose or preparation method 
      • Clinical Meaning:
        • Low-dose RAI + rhTSH is as effective as high-dose with withdrawal
        • Lower toxicity, better patient convenience:
          • Incorporated in ATA 2015 guidelines (New Guidelines Coming Out Fall 2025)
    • HiLo (UK, Mallick et al., 2012):
      • Design:
        • Similar to ESTIMABL1:
          • Compared low- vs high-dose plus rhTSH vs withdrawal
      • Outcome:
        • Comparable ablation success and low recurrence rates 
    • ESTIMABL2 (France, 2022):
      • Design:
        • RCT of low-dose RAI (1.1 GBq) vs no RAI, post-total thyroidectomy in low-risk DTC
      • 3-Year Results:
        • Recurrence:
          • 2.7% (no RAI) vs 1.9% (RAI); non-inferior 
      • Commentary:
        • Non-inferiority holds even at lowest end of risk spectrum:
          • Upholds omission in select patients
    • IoN (“Iodine or Not”) Trial (UK, Lancet June 2025):
      • Design:
        • Phase II / III RCT randomizing 504 low-risk DTC patients to RAI vs no RAI
      • 5-Year Data:
        • 98% disease-free without RAI vs 96% with RAI
        • Omitting RAI improved quality of life and reduced isolation burden 
      • Significance:
        • Largest definitive trial confirming RAI omission is safe in ATA low-risk patients
    • Additional Evidence and Observational Data:
      • Long-term observational studies (> 8 years):
        • Show high remission and low recurrence with low-dose RAI 
      • Meta-analyses and reviews echo findings:
        • Low-dose or no RAI yields excellent oncologic outcomes in strictly low-risk DTC
  • Clinical Take‑Home Points for Surgeons:
    • Low-dose (1.1 GBq) RAI is sufficient for remnant ablation when RAI is used
    • rhTSH is preferred for patient comfort
    • RAI omission is safe in ATA low-risk cases:
      • Per ESTIMABL2 and IoN with:
        • ~ 98% disease-free survival at 5 years
      • QoL benefit and reduced isolation burden when RAI is not used:
        • Especially relevant for younger, family-centered patients
    • ATA 2015 guidelines:
      • Support selective RAI omission, reinforced by current trials
    • Surgical completeness matters:
      • Trials include total thyroidectomy with low /absent nodal burden
      • Partial thyroidectomy or residual disease was excluded
    • Follow-up protocol:
      • Stringent ultrasound and thyroglobulin monitoring essential when omitting RAI
  • Practical ATA-Based Approach:
    • Very Low / Low Risk ATA:
      • Intrathyroidal ≤ 4 cm
      • N0 to N1a
      • No vascular invasion:
        • Omit RAI:
          • Active surveillance with US + Tg (with / without rhTSH)
      • If ablation desired (e.g., Tg monitoring ease):
        • Use 1.1 GBq + rhTSH
    • Intermediate Risk:
      • Minimal extrathyroidal extension
      • > 5 involved nodes:
        • Consider selective RAI at low dose:
          • Decision individualized based on risk tolerance
  • Summary:
    • In ATA-defined low-risk DTC:
      • Low-dose RAI + rhTSH is as effective as high-dose or withdrawal methods
    • Importantly, omission of RAI does not compromise outcomes and offers QoL and cost benefits
    • Surveillance replaces ablation, with triggers reserved for structural or biochemical recurrence
#Arrangoiz #CancerSurgeon #ThyroidSurgeon
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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