What are the main purposes of radioactive iodine (¹³¹I) therapy in differentiated thyroid cancer treatment?

After a thyroidectomy for differentiated thyroid cancer, radioactive iodine (¹³¹I) therapy is often employed. It can be used for different purposes: to eliminate remaining thyroid tissue (remnant ablation), to address suspected but not confirmed residual disease (adjuvant treatment), or to treat known residual or recurrent disease. This decision influences future outcomes and is crucial in managing the disease.

What is the difference between remnant ablation and adjuvant therapy using radioactive iodine (¹³¹I)?

Remnant ablation aims to destroy any remaining benign thyroid tissue after surgery using radioactive iodine (¹³¹I). The effectiveness is determined by the absence of persistent thyroid cells, typically evaluated 6–12 months post-ablation. In contrast, adjuvant therapy, also using ¹³¹I, is given to patients at risk of recurrence even if no disease is currently detectable. Adjuvant therapy's success is measured by improved disease-specific survival and reduced structural recurrence.

What were the main findings of the HiLo and ESTIMABL1 trials regarding remnant ablation?

Two major trials, HiLo and ESTIMABL1, demonstrated the effectiveness of using either thyroid hormone withdrawal or recombinant human thyroid-stimulating hormone (rhTSH) combined with specific ¹³¹I activities for remnant ablation. These studies found that remnant ablation was successful in a high percentage of patients (85-95%). The choice between these methods doesn't affect the underlying treatment goals.

How does the success of remnant ablation impact the long-term outcomes for patients with thyroid cancer?

The success of remnant ablation has a significant impact on long-term outcomes. If remnant ablation is successful, the rate of persistent or recurrent structural disease is significantly lower (less than 1%). Conversely, patients with unsuccessful remnant ablation have a much higher rate of persistent or recurrent disease, as highlighted by the HiLo trial. This outcome underscores the importance of initial treatment strategies on future health.

What is the significance of the HiLo and ESTIMABL1 trials for future thyroid cancer management?

The HiLo and ESTIMABL1 trials provide crucial insights into the preparation and optimal use of ¹³¹I for remnant ablation. These findings should be used to design future clinical trials for adjuvant treatment. The article emphasizes the need for further research to determine the most effective strategies for adjuvant therapy, especially in low- to intermediate-risk patients, which requires larger studies due to the anticipated low rates of disease recurrence and mortality.

Butterfly emerging from thyroid gland, representing thyroid cancer transformation.

Thyroid Cancer Treatment: How Remnant Ablation Impacts Long-Term Outcomes

Nico Varela in Health & Wellness December 2025 • 4 min read.

"A deeper look into differentiating remnant ablation from adjuvant treatment in differentiated thyroid cancer and its implications for recurrence."

In the treatment of differentiated thyroid cancer, radioactive iodine (¹³¹I) therapy plays a crucial role after thyroidectomy. This therapy is administered with varying intentions: to eliminate any remaining benign thyroid tissue in the thyroid bed (remnant ablation), to target suspected but unconfirmed residual disease (adjuvant treatment), or to address known residual or recurrent disease (treatment of known disease).

Unlike treating known disease, adjuvant ¹³¹I therapy is administered based on risk rather than confirmed persistent disease. Remnant ablation's success is gauged by the absence of persistent thyroid cells, evident 6–12 months post-ablation. Conversely, the efficacy of adjuvant therapy is assessed by improvements in disease-specific survival and reduced structural disease recurrence rates. Managing known disease focuses on slowing disease progression, maintaining quality of life, and extending survival.

Two pivotal randomized non-inferiority trials, HiLo and ESTIMABL1, have demonstrated that either thyroid hormone withdrawal or recombinant human thyroid-stimulating hormone (rhTSH), combined with ¹³¹I activities of 1.1 GBq or 3.7 GBq, effectively achieve successful remnant ablation in 85-95% of patients.

Long-Term Impact of Initial ¹³¹I Activity on Thyroid Cancer Recurrence

Butterfly emerging from thyroid gland, representing thyroid cancer transformation.

Hakim-Moulay Dehbi and colleagues reported the long-term outcomes of the HiLo trial, assessing the impact of the initial ¹³¹I activity when used for adjuvant treatment or to treat known disease. The study focused on the rates of persistent disease (biochemical or structural evidence of disease remaining after initial therapy) or recurrent disease (biochemical or structural disease identified after initial therapy).

The HiLo and ESTIMABL1 trials confirm previous observations of structural disease persistence and recurrence rates being less than 5% in patients with low to intermediate risk differentiated thyroid cancer. Both trials underscore the necessity of modifying risk estimates following initial therapy, given that the rate of recurrent and persistent structural disease in patients who achieved successful remnant ablation dropped to less than 1%.

Patients without successful ablation had a 15% diagnosis rate of persistent or recurrent disease.
The HiLo trial revealed that recurrent or persistent structural disease was detected earlier in patients without successful ablation.
The success or failure of remnant ablation, evaluated as early as 6–9 months post-initial therapy, should guide the modification of the frequency and intensity of follow-up based on initial American Thyroid Association (ATA) risk stratification.

The trials are primarily designed and powered to assess the efficacy of remnant ablation in low to intermediate risk patients, the trials cannot provide definitive answers about the need for, or efficacy of, ¹³¹I therapy given primarily for adjuvant treatment. Properly designed adjuvant therapy trials in low to intermediate risk patients will necessitate larger sample sizes and longer follow-up periods due to anticipated low event rates (disease-specific mortality <1% and structural disease recurrence rates of <10%).

Future Directions in Thyroid Cancer Management

The HiLo and ESTIMABL1 trials offer valuable insights into preparation methods and ¹³¹I activities for remnant ablation. As such, the thyroid cancer community should use these trials to design prospective, randomized clinical trials to assess the efficacy and optimal ¹³¹I activity for adjuvant treatment.

Patient selection for adjuvant treatment trials should consider initial risk stratification and a thorough evaluation of disease status post-initial surgery. This careful approach is necessary to differentiate the potential role of ¹³¹I therapy in treating known persistent disease from its role in true adjuvant treatment.

Ongoing trials, such as the IoN trial (NCT01398085) and ESTIMABL2 (NCT01837745), are poised to further refine our understanding of persistent and recurrent disease rates, particularly in patients undergoing low-dose ¹³¹I or observation after total thyroidectomy.