The role of radioactive iodine therapy after total thyroidectomy in aggressive variant papillary thyroid carcinoma

Background: Radioactive iodine (RAI) is commonly administered after thyroidectomy, but its efficacy in aggressive variants of papillary thyroid carcinoma (AVPTC), particularly the tall/columnar cell subtypes, remains uncertain. This study aims to identify the patient subgroups most likely to benefit from RAI treatment. Method: Using SEER data (2000–2015), we analyzed 946 AVPTC patients who underwent total thyroidectomy with a follow-up of at least three years. Restricted cubic spline (RCS) analysis was employed to identify non-linear prognostic thresholds for age and metastatic lymph node count. Other variables included tumor size, multifocality, and distant metastasis. Cancer-specific survival (CSS) was compared between the ATA guideline-based groups and a novel RCS-stratified model. Results: Among 946 patients, there was no significant CSS difference between the ATA-recommended (n = 818) and non-recommended (n = 128) groups (p > 0.05). RCS analysis identified age >50 years and >3 metastatic lymph nodes as critical thresholds for increased mortality risk. A model incorporating these thresholds significantly outperformed the ATA classification (C-index: 0.77 vs. 0.56). RAI treatment improved CSS in patients >50 years old with >3 metastatic nodes or distant metastasis (multivariate HR = 0.30, p < 0.01), but not in lower-risk subgroups. Conclusions: Age >50 years and >3 metastatic lymph nodes are key prognostic factors for high-risk AVPTC patients who benefit from RAI. This individualized approach, based on non-linear risk stratification, offers an optimized alternative to routine adjuvant RAI protocols.