Reassessing Radioactive Iodine Use After Thyroidectomy in Low-Risk Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND

Radioactive iodine (RAI) therapy is often administered post-total thyroidectomy in patients with low-risk differentiated thyroid carcinoma, despite guidelines advising against its routine application. Evidence regarding the efficacy of RAI in reducing recurrence and improving survival in low-risk differentiated thyroid cancer (DTC) remains inconsistent.

METHODS

We conducted a systematic review and meta-analysis of observational studies and randomized clinical trials that compare RAI versus no RAI in low-risk DTC patients. Databases such as MEDLINE, Scopus, Cochrane Library, and Google Scholar were searched through December 2025. Outcomes included recurrence, recurrence-free survival, treatment response, biochemical markers, and side effects. We performed statistical analysis using Review Manager (RevMan) 5.4 with a random-effects model, reporting odds ratios (OR) with 95% confidence intervals, and significance set at p < 0.05. Heterogeneity was assessed using I² statistics.

RESULTS

Ten studies (n = 5260) were included in the analysis. No statistically significant difference was observed between the two groups for recurrence (OR 0.66, 95% CI: 0.41-1.08; p = 0.10), 5-year recurrence-free survival (OR 2.47, 95% CI: 0.63-9.62; p = 0.19), or treatment response (excellent response: OR 1.00, 95% CI: 0.52-1.92; p = 1.00). Secondary outcomes, including serum thyroglobulin > 1 ng/mL (OR 1.20, 95% CI: 0.00-342.55; p = 0.95), elevated thyroglobulin antibodies (OR 0.91, 95% CI: 0.38-2.16; p = 0.83), xerostomia (OR 5.63, 95% CI: 0.05-667.24; p = 0.48), and dysphonia (OR 0.96, 95% CI: 0.53-1.72; p = 0.88), were also not significantly different between groups, although estimates were not precise.

CONCLUSION

The available randomized and observational evidence does not demonstrate a clear, clinically meaningful benefit of routine RAI ablation in patients classified as low-risk DTC. These findings should be interpreted with caution due to heterogeneity across studies, variability in outcome definitions, and the predominance of observational data.

© 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.