AUTHOR=Xu Ming-Lu , Wang Yang-Yang , Xie Li-Ping , Ding Ning , Hui Jia-Jun TITLE=Liver metastases in thyroid cancer: epidemiology, risk stratification and survival outcomes in the immunotherapy era JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1624181 DOI=10.3389/fimmu.2025.1624181 ISSN=1664-3224 ABSTRACT=PurposeLiver metastases in thyroid cancer are rare but fatal, with poorly defined risk profiles and survival outcomes. This study aimed to characterize epidemiology, risk factors and outcomes of this disease using a population-based approach, further explore the potential impact of the immunotherapy era on the prognosis of these patients.MethodsData on 116,801 thyroid cancer cases from SEER program (2010-2021) were analyzed. The clinicopathological features of patients with and without liver metastases were compared. Logistic regression analyses were employed to identify the predictors for liver metastases, while survival determinants were determined using Cox regression models. The predictive nomogram was developed for liver metastasis risk assessment, validated using concordance index, calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). In addition, we further compared the prognostic outcomes of these patients in the immunotherapy era.ResultsThe prevalence of liver metastasis in thyroid cancer was 0.22% (95%CI 0.20%-0.25%), predominantly in medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC). MTC exhibited the highest risk of metastasis (OR=35.7, 95%CI 24.1–52.8). The nomogram for liver metastasis risk (C-index=0.98) demonstrated robust discriminatory ability and clinical utility. The median overall survival (OS) was 6.0 months (95%CI 4.0–8.0), with survival rates of 38.1% at 1 year, 28.3% at 3 years, and 16.5% at 5 years. Patients with ATC and rare histology types experienced significantly shorter survival. No statistically significant difference in mOS and median cancer-specific survival (mCSS) of these patients between the pre- and post-immunotherapy eras were observed (P>0.05 for both).ConclusionThis study establishes the first population-based predictive framework for liver metastases in thyroid cancer, underscoring risk stratification and survival. These findings also highlight the critical need to optimize survival outcomes for this aggressive metastatic phenotype in immunotherapy era.