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

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. 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. 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. 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.