Analysis of prognostic factors related to pulmonary metastasectomy for hepatocellular carcinoma following liver resection.

[BACKGROUND] Pulmonary metastasectomy improves survival in selected patients with malignancies such as colorectal carcinoma and osteosarcoma. As the most common site of extrahepatic recurrence in hepatocellular carcinoma (HCC), pulmonary metastases are increasingly considered for surgical resection. However, the criteria for patient selection and the indications for surgery remain poorly defined. This study aimed to identify prognostic factors to guide patient selection for pulmonary metastasectomy in HCC.

[METHODS] We conducted a retrospective analysis of 46 HCC patients who underwent pulmonary metastasectomy at our institution between January 2015 and January 2022. Progression-free survival (PFS) and overall survival (OS) were analyzed to identify prognostic factors. The predictive performance of independent factors was evaluated using receiver operating characteristic (ROC) curves. Immunohistochemical staining for molecular markers was performed on primary HCC tissues from 33 patients to assess their prognostic value.

[RESULTS] Among the 46 patients, 29 (63.0%) experienced recurrence after metastasectomy. The median PFS was 9.2 months, with a median follow-up of 28.5 months. Univariate analysis identified a disease-free interval (DFI) > 12 months ( < 0.001) and histological grade 2 ( = 0.042) as significant predictors of improved PFS, while a maximum pulmonary metastasis diameter ≤ 1.3 cm ( = 0.003) was associated with improved OS. Multivariate analysis confirmed DFI > 12 months as an independent prognostic factor for PFS ( = 0.006), and both DFI > 12 months ( = 0.047) and pulmonary metastasis diameter ≤ 1.3 cm ( = 0.003) for OS. ROC analysis demonstrated that the combination of DFI (AUC = 0.752) and metastasis diameter (AUC = 0.708) provided superior predictive value for OS (AUC = 0.771;  = 0.007). Furthermore, high CD8+ ( = 0.037), low CD68+ ( = 0.045), and FOXP3+ ( = 0.036) expression in primary HCC were significantly associated with better PFS and remained independent prognostic factors in the multivariate model.

[CONCLUSIONS] A DFI > 12 months and a maximum pulmonary metastasis diameter ≤ 1.3 cm are independent prognostic factors in HCC patients undergoing pulmonary metastasectomy, and their combination provides excellent predictive value. An immune-favorable microenvironment in the primary tumor is also associated with improved outcomes. These findings support aggressive surgical management of pulmonary metastases in carefully selected HCC patients.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s12672-026-04606-z.