Radioactive Iodine in Differentiated Thyroid Cancer: Effect on Detection of Distant Metastases Comparing 4 Guidelines

Abstract

Context: Guidelines vary in their recommendations for postoperative radioactive iodine (RAI) in differentiated thyroid cancer (DTC). Omitting RAI reduces overtreatment but poses the possibility of missing distant metastases. Objective: This study compares 4 guidelines on RAI indications and potentially missed metastases. Methods: DTC patients were included retrospectively, including 48 patients with distant metastases after first RAI cycle, and 469 without distant metastases. The percentage of distant metastases missed was calculated if RAI had been omitted following the 2015 American Thyroid Association (ATA), 2019 European Society for Medical Oncology (ESMO), 2022 European Thyroid Association (ETA), and 2022 American Society of Nuclear Medicine and Molecular Imaging/European Association of Nuclear Medicine (SNMMI/EANM) guidelines. Results: In patients without RAI indication, 1.3% to 1.6% of distant metastases may initially be missed with the ATA, ESMO, and ETA guidelines. All these cases had postoperative thyroglobulin (Tg) between 1 and 10 ng/mL or positive Tg antibodies (Tg-abs). In patients for whom RAI should be considered following the ATA, ESMO, and ETA guidelines, 2.6% to 4.0% of distant metastases may initially be missed, with all but 1 case having Tg greater than 10 ng/mL or positive Tg-abs. With the SNMMI/EANM guideline, no distant metastases would be missed, but it resulted in markedly higher RAI use in low-risk patients (82% vs 0%). Conclusion: Omitting postoperative RAI in low- and intermediate-risk patients, as recommended by the 2015 ATA, 2019 ESMO, and 2022 ETA guidelines, may lead to a small number of initially undetected distant metastases. However, these metastases could potentially be detected later due to the presence of biochemical disease. In contrast, the broader RAI indications endorsed by SNMMI/EANM reduce the likelihood of missed metastases, but substantially increases RAI use, exposing patients to unnecessary treatment and side effects.