Purpose: Locally advanced thyroid cancer (LATC) has gained increased attention, yet factors influencing invasion patterns and their prognostic impact remain poorly understood.

Methods: Patients with LATC were identified from the Surveillance, Epidemiology, and End Results (SEER) program. Invasion patterns were visualized using bar graphs. Kaplan-Meier method and log-rank test analyzed outcomes by different invasion sites. Multivariable Cox regression analysis was conducted to adjust confounding factors and establish a new site-based risk stratification.

Results: Papillary thyroid carcinoma (PTC) predominantly invaded esophagus or larynx (21.0%) and trachea (26.3%), while follicular thyroid carcinoma/oncocytic thyroid carcinoma (FTC/OTC) mainly invaded blood vessel (31.3%). Anaplastic thyroid carcinoma (ATC) exhibited the highest rate of trachea invasion (33.3%) and multi-invasion (8.1%). Age, tumor size significantly influenced the proportion of trachea invasion (p < 0.001). Locally advanced PTC patients with different invasion sites demonstrated significantly different prognoses: 10-year OS rate of each invasion site was: parathyroid or nerve (82.5%), bone or skeletal muscle (76.6%), esophagus or larynx (68.7%), blood vessel (58.0%), trachea (57.5%), multi-invasion (26.8%). Based on multivariable Cox regression, a novel site-based risk stratification was established for locally advanced PTC patients, with trachea invasion (HR = 1.83, p < 0.001), blood vessel invasion (HR = 2.64, p < 0.001), and multi-invasion (HR = 2.76, p < 0.001) categorized as medium and high risk of mortality, respectively, demonstrating better discrimination than 8th AJCC staging system.

Conclusion: This study is the first to utilize population-based cohort to reveal factors influencing invasion sites and their prognostic differences. This study also proposed a new site-based risk stratification that builds upon 8th AJCC T staging for locally advanced PTC patients, which may facilitate more tailored clinical management strategies.

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http://dx.doi.org/10.1007/s12020-025-04165-3DOI Listing

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