- Title:
- Outcome after ablation in patients with low‑risk thyroid cancer (ESTIMABL1)
- Design:
- A multicenter, randomized, open-label, phase III equivalence trial:
- Across 24 centers in France (2007 to 2010)
- A multicenter, randomized, open-label, phase III equivalence trial:
- Population:
- 752 adults with low-risk papillary or follicular differentiated thyroid cancer (DTC) post-total thyroidectomy
- Randomization (1:1:1:1) into four groups:
- RAI dose:
- Low (1.1 GBq / ~30 mCi) vs High (3.7 GBq / ~100 mCi)
- TSH stimulation:
- rhTSH injections vs thyroid hormone withdrawal
- RAI dose:
- Primary Endpoint:
- Successful remnant ablation at 6 to 10 months:
- Defined as stimulated thyroglobulin ≤ 1 ng/mL and no residual tissue on ultrasound
- Successful remnant ablation at 6 to 10 months:
- Initial and Long-Term Efficacy:
- 6 to 10 Month Ablation Success:
- ~ 92% across all groups:
- With equivalence between:
- Low and high dose
- rhTSH vs withdrawal
- With equivalence between:
- ~ 92% across all groups:
- 5.4-Year Median Follow-Up (n = 726):
- 98% had no evidence of disease (715 / 726)
- 11 patients had evidence of persistent or recurrent disease (structural or biochemical)
- Recurrence was evenly distributed across RAI dose and stimulation method:
- Indicating no impact of strategy on long-term outcomes
- Recurrence was evenly distributed across RAI dose and stimulation method:
- 6 to 10 Month Ablation Success:
- Prognostic Predictors:
- Stimulated thyroglobulin at ablation:
- Was predictive of eventual disease status and ablation success:
- Patients with higher thyroglobulin were more likely to have persistent disease regardless of group
- Was predictive of eventual disease status and ablation success:
- No lymph node stratification influence or stimulation method effect was observed
- Stimulated thyroglobulin at ablation:
- Clinical Implications:
- Low-dose RAI (1.1 GBq) with rhTSH is validated as standard of care:
- Equivalent efficacy with better patient experience
- ATA 2015 guidelines endorse this strategy for low-risk DTC:
- Simplified staging and reduced toxicity
- No impact on long-term disease-free survival:
- Supports tailored management based on disease biology rather than RAI intensity
- Low-dose RAI (1.1 GBq) with rhTSH is validated as standard of care:
- Evidence Synthesis:
- Meta-analysis of RCTs (> 1,500 patients, 4 to 10 years follow-up):
- Confirms no difference in long-term recurrence between 1.1 GBq and 3.7 GBq (OR 0.93, 95% CI 0.53–1.63)
- Similar equivalence was seen between rhTSH vs hormone withdrawal and across centers (France & UK)
- HiLo trial results align, confirming comparable recurrence rates with low-dose RAI and rhTSH
- Meta-analysis of RCTs (> 1,500 patients, 4 to 10 years follow-up):
- Surgical Take-Home Points:
- Remnant ablation using low-dose RAI + rhTSH is effective and minimizes side effects compared to high-dose or withdrawal strategies
- Stimulated thyroglobulin at post-op ablation is a stronger predictor of recurrence than RAI dose or preparation method
- No difference in long-term disease-free survival across dose or stimulation arms supports risk-adapted RAI use
- Multidisciplinary protocols should adopt low-dose rhTSH-based ablation for ATA low-risk patients, reserving higher dose only for select cases (e.g., unresected tissue, aggressive pathology)
- Surveillance strategies:
- Regular ultrasound + Tg on levothyroxine; use stimulated Tg selectively for indeterminate findings
Rodrigo Arrangoiz MS, MD, FACS, FSSO 