Multiplication of Alpha-Fetoprotein and Protein Induced by Vitamin K Absence-II is Associated with Prognosis After Pulmonary Metastasectomy in Hepatocellular Carcinoma.

BACKGROUND/PURPOSE: The role of pulmonary metastasectomy for hepatocellular carcinoma (HCC) has declined with the advent of effective systemic therapies, but selected patients may still benefit from surgical treatment. The AP factor, defined as alpha-fetoprotein (AFP) × protein induced by vitamin K absence-II (PIVKA-II), has been proposed as a prognostic biomarker for HCC. This study evaluated the association between the AP factor and outcomes in patients undergoing pulmonary metastasectomy for recurrent HCC after hepatectomy.

METHODS

We retrospectively analyzed patients who underwent resection of pulmonary metastases after hepatectomy for HCC between 1990 and 2025. Patients with uncontrolled intrahepatic disease, non-curative resection, extra-pulmonary metastases, or missing tumor marker data were excluded. Overall survival (OS) and recurrence-free survival (RFS) after lung resection were analyzed using the log-rank test. Multivariate analysis was performed using Cox proportional hazards models.

RESULTS

Forty-three patients underwent pulmonary metastasectomy. The median follow-up period was 3.6 years. The 5-year OS and RFS rates were 46.4% and 8.0%, respectively, with a median OS of 51.8 months. An AP factor ≥100,000 was associated with markedly poor survival (5-year OS 0.0% vs. 51.1%, p<0.0001). Multivariate analysis identified an AP factor ≥100,000 as an independent predictor of OS (p=0.010), whereas AFP ≥500 ng/mL independently predicted RFS (p=0.036).

CONCLUSIONS

The AP factor is associated with overall survival in patients undergoing pulmonary metastasectomy for recurrent HCC. Patients with an AP factor ≥100,000 have extremely poor outcomes after surgery, suggesting that careful patient selection for surgical resection is warranted.