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

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) / Pulmonary metastasis (PM) / Pulmonary metastasectomy / Immunotherapy / Targeted therapy

Authors’ contributions

Juxian Sun, Chang Liu, and Xiandong Tao contributed equally to this paper and should be considered co-first authors. Juxian Sun: Writing e original draft, Methodology, Data curation, Conceptual-ization. Chang Liu: Writing e original draft, Methodology, Data curation. Xiandong Tao: Writing e review & editing, Methodology, Investigation, Data curation. Yu Yang: Writing e review & editing, Methodology, Data curation. Hai Jin: Writing e review & editing, Data curation. Shuqun Cheng: Writing e review & editing, Meth-odology, Funding acquisition. Huazheng Shi: Writing e review & editing, Supervision, Methodology, Data curation. Maolin Yan: Writing e review & editing, Supervision, Methodology, Data cura-tion, Conceptualization. Jie Shi: Writing e review & editing, Su-pervision, Methodology, Funding acquisition, Conceptualization. All authors approved the final version of the manuscript for publication.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. Research data are not shared, owing to the privacy or ethical restrictions.

Declaration of competing interest

The authors declare that they have no conflict of interest.

Acknowledgements

This work is supported by the School-level project of Naval Medical University (No. 2022MS038); National Natural Science Foundation of China (No.82073293); National Key R&D Program of China (No.2022YFC2503700).

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