Prognostic comparison between pulmonary metastasectomy and combination immunotherapy with targeted molecular therapies for advanced hepatocellular carcinoma with pulmonary metastasis: A propensity score matching analysis

Juxian Sun; Chang Liu; Xiandong Tao; Yu Yang; Hai Jin; Shuqun Cheng; Huazheng Shi; Maolin Yan; Jie Shi

doi:10.1016/j.livres.2025.01.006

Prognostic comparison between pulmonary metastasectomy and combination immunotherapy with targeted molecular therapies for advanced hepatocellular carcinoma with pulmonary metastasis: A propensity score matching analysis

Liver Res. 2025 Jan 30;9(1):29-35. doi: 10.1016/j.livres.2025.01.006. eCollection 2025 Mar.

Authors

Juxian Sun¹, Chang Liu¹, Xiandong Tao², Yu Yang³, Hai Jin⁴, Shuqun Cheng¹, Huazheng Shi⁵, Maolin Yan⁶, Jie Shi¹

Affiliations

¹ Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
² Department of Thoracic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
³ Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
⁴ Department of Thoracic Surgery, Changhai Hospital of Shanghai, Naval Medical University, Shanghai, China.
⁵ Shanghai University Cloud Medical Imaging Diagnostic Center, Shanghai, China.
⁶ Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian, China.

Abstract

Background and aims: Advanced hepatocellular carcinoma (HCC) with pulmonary metastasis (PM) has a poor prognosis, and optimal treatment strategies remain controversial. This study aimed to compare the long-term outcomes of patients with advanced HCC with PM who were treated with resection of pulmonary metastases versus those treated with targeted therapies combined with immunotherapy.

Methods: A retrospective analysis was conducted on the medical records of HCC patients with PM who underwent either pulmonary metastasectomy or immunotherapy combined with targeted therapies at the Eastern Hepatobiliary Surgery Hospital, Changhai Hospital of Shanghai, Fujian Provincial Hospital, and West China Hospital of Sichuan University from September 2013 to October 2022. One-to-one propensity score matching (PSM) was employed to control the influence of potential confounders, and the survival outcomes were compared.

Results: A total of 119 HCC patients with PM were included in this study. The overall survival (OS) of patients who underwent pulmonary metastasectomy was significantly longer than that of patients who received immunotherapy targeted combinations (OS: 1-year, 80.0% vs. 59.3%; 2-year, 31.7% vs. 20.3%; 3-year, 20.0% vs. 0; P < 0.001). After PSM, the long-term prognosis of the pulmonary metastasectomy group remained significantly better than that of the immunotherapy combination group (OS: 1-year, 87.0% vs. 69.6%; 2-year, 34.8% vs. 30.4%; 3-year, 21.7% vs. 0; P = 0.005). Multivariate analysis revealed that treatment allocation (hazard ratio (HR) = 2.177, 95% confidence interval (CI) = 1.068-4.439) and hepatic tumor T stage (HR = 2.342, 95% CI = 1.209-4.538) were independent risk factors for OS.

Conclusions: Pulmonary metastasectomy was associated with improved survival compared to immunotherapy combined with targeted therapies and may represent an optimal treatment option for highly selected HCC patients with resectable PM.

Keywords: Hepatocellular carcinoma (HCC); Immunotherapy; Pulmonary metastasectomy; Pulmonary metastasis (PM); Targeted therapy.