Moderate- Versus High-Activity Radioactive Iodine in Intermediate-Risk Papillary Thyroid Cancer: A Canadian Cohort Study

Abstract Context The optimal radioactive iodine (RAI) activity for intermediate-risk papillary thyroid cancer (PTC) remains uncertain, and evidence to guide individualized treatment is limited. Objective To compare recurrence between moderate- and high-activity RAI and to identify clinicopathologic factors associated with persistent or recurrent disease. Design Retrospective cohort study. Setting Tertiary academic thyroid cancer clinic Patients Adults with intermediate-risk PTC treated between 2010 and 2022. Intervention Moderate- (30 to 90 mCi) vs high-activity RAI (>90 mCi) as initial postoperative therapy. Main Outcome Measure(s) Primary outcome: time to recurrence. Secondary outcome: composite of persistent or recurrent disease at last follow-up. Results Among 181 patients, 94 received moderate-activity RAI and 87 received high-activity RAI. Over a median follow-up of 52 months, 18 recurrences occurred (crude: 3/94 vs 15/87). High-activity RAI was not associated with improved recurrence-free survival (inverse probability of treatment weighting [IPTW]-weighted hazard ratio 2.73; 95% confidence interval [CI] 0.74 to 10.01). Persistent or recurrent disease occurred in 61 patients (34%) with no association in IPTW models (hazard ratio 0.97; 95% CI 0.53 to 1.76). Extranodal extension, microscopic extrathyroidal extension, larger lymph node deposit size, and older age were associated with persistent or recurrent disease. Conclusions High-activity RAI was not associated with improved recurrence versus moderate-activity in intermediate-risk PTC. This study is among the first to evaluate moderate-activity RAI as a distinct comparator. Findings support moderate-activity RAI as a reasonable risk-adapted approach. Prospective studies are needed to validate these results.