- Trial Overview – ESTIMABL2 (NCT01837745):
- Is a French, multicenter, phase III randomized trial investigating the necessity of post-thyroidectomy radioactive iodine (RAI) in patients with low-risk DTC:
- Defined as intrathyroidal papillary carcinomas ≤ 1 cm (pT1a-m) or 1 to 2 cm (pT1b), with no suspicious lymph nodes on preoperative neck ultrasound (N0 / Nx)
- All underwent total thyroidectomy (with or without prophylactic central neck dissection) and were randomized at 2 to 5 months post-op to:
- RAI group:
- 1.1 GBq (30 mCi) after rhTSH preparation
- No‑RAI group:
- Surveillance only
- RAI group:
- Follow-up Protocol:
- 3-year endpoint:
- Thyroglobulin (Tg) and anti-Tg antibodies annually, neck ultrasound in alternating years
- 3-year endpoint:
- Event definition:
- Need for further radioactive iodine or surgery:
- Due to abnormal uptake, ultrasound changes, Tg rise, or antibody surge
- Non-inferiority margin:
- 5% difference in event-free survival
- Need for further radioactive iodine or surgery:
- Primary (3-Year) Results:
- Evaluable patients:
- 729 (FU: 367; RAI: 362)
- Events:
- 18 (4.9%) in surveillance vs 15 (4.1%) in RAI
- Event-free survival:
- 95.1% (no RAI) vs 95.9% (RAI)
- Difference 0.8% (95% CI –3.3% to 1.8%) → non-inferiority confirmed
- Evaluable patients:
- Secondary interventions (surgery / RAI):
- 6 (1.6%) vs 9 (2.5%)
- Is a French, multicenter, phase III randomized trial investigating the necessity of post-thyroidectomy radioactive iodine (RAI) in patients with low-risk DTC:
- 5-Year Long-Term Outcomes:
- Evaluable at 5 years:
- 698 patients
- Event-free survival:
- No RAI: 93.2%
- RAI: 94.8%
- Difference: 1.6% (90% CI –4.5 to 1.4%)
- Remains within non-inferiority bounds
- Difference: 1.6% (90% CI –4.5 to 1.4%)
- Evaluable at 5 years:
- Quality of response:
- Surveillance group had higher rates of “excellent response” (83.3% vs 75.6%) and fewer indeterminate results
- Clinical Implications for Surgeons:
- Omission of adjuvant RAI in strictly defined ATA low-risk patients (pT1, cN0, complete surgery, normal Tg and US) is safe and effective, even at 5 years
- Non-inferiority margin of 5% comfortably met at both 3 and 5 years, a robust outcome
- Superior biochemical and imaging outcomes in the surveillance arm suggest less overdiagnosis and overtreatment
- Reduces patient burden:
- Avoids radiation, isolation, and enhances convenience
- Supports tailored management:
- RAI can be reserved for cases with unfavorable histology, remnant tissue on US, or rising Tg / antibodies
- Recommendations for Practice:
- Strict selection is essential:
- Only patients with pT1 N0 / Nx, complete surgery, and negative post-op US are eligible for RAI omission
- Omit RAI in these low-risk patients, with follow-up consisting of Tg, TgAb, and periodic neck ultrasound
- Reserve RAI for patients with adverse features:
- Aggressive histology
- Tg rise
- Suspicious imaging
- Discuss care pathway in MDT rounds, highlighting QoL gains and similar oncologic outcomes
- Educate patients:
- Provide clear rationale and plan for surveillance to avoid anxiety over omitted therapy
- Strict selection is essential:
- Final Takeaways:
- The ESTIMABL2 trial delivers strong evidence that surveillance alone post-thyroidectomy is a safe, effective, and patient-centric strategy in carefully selected ATA low-risk DTC patient:
- Offering similar long-term outcomes to standard RAI treatment, with additional QoL and diagnostic benefits
- The ESTIMABL2 trial delivers strong evidence that surveillance alone post-thyroidectomy is a safe, effective, and patient-centric strategy in carefully selected ATA low-risk DTC patient:
Rodrigo Arrangoiz MS, MD, FACS, FSSO 