# Liver metastases in thyroid cancer: epidemiology, risk stratification and survival outcomes in the immunotherapy era

## TL;DR

This study examines liver metastases in thyroid cancer, identifying risk factors and survival outcomes using population data and a predictive model.

## Contribution

The study introduces the first population-based predictive framework for liver metastases in thyroid cancer.

## Key findings

- Liver metastases occurred in 0.22% of thyroid cancer cases, most commonly in medullary and anaplastic thyroid carcinomas.
- A high-performance nomogram was developed for liver metastasis risk assessment with strong discriminatory ability.
- Survival rates were low, with no significant improvement observed in the immunotherapy era.

## Abstract

Liver 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.

Data 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.

The 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).

This 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.