The Prognostic Nutritional Index (PNI) as a Biomarker for Predicting Survival in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization and Lenvatinib, With or Without Programmed Death-1(PD-1) Inhibitors.

[PURPOSE] Current treatment strategies for hepatocellular carcinoma (HCC) using transarterial chemoembolization (TACE) combined with lenvatinib and immunotherapy remain largely empirical due to the lack of reliable biomarkers. This study aimed to evaluate the prognostic significance of the Prognostic Nutritional Index (PNI) in HCC patients treated with TACE plus lenvatinib, with or without programmed death-1 (PD-1) inhibitors.

[MATERIALS AND METHODS] We conducted a retrospective analysis of 237 patients with HCC who received TACE and lenvatinib-based therapy, with or without PD-1 inhibitors, between March 2021 and September 2023. Patients were randomly allocated into training and validation sets in a 7:3 ratio and stratified into low- and high-PNI groups based on an optimal PNI cut-off value. Overall survival (OS) and progression-free survival (PFS) were compared between the PNI groups using the log-rank test.

[RESULTS] In both the training and validation sets, patients with higher PNI scores demonstrated significantly better OS and PFS than those with lower PNI scores. Multivariate Cox regression identified PNI score, treatment modality (TACE + lenvatinib ± PD-1 inhibitor), tumor diameter, alpha-fetoprotein (AFP), and alanine aminotransferase (ALT) as independent prognostic factors for OS. For PFS, independent predictors included PNI score, treatment modality, tumor diameter, Child-Pugh class, and AFP level. Subgroup analyses consistently showed superior OS in the high-PNI group across most strata, including those defined by treatment type, presence of portal vein tumor thrombosis (PVTT) or extrahepatic metastasis (EHM), AFP level (≤ 400 or > 400 ng/mL), and Barcelona Clinic Liver Cancer (BCLC) stage C.

[CONCLUSION] The PNI score is a promising biomarker for predicting survival in HCC patients receiving TACE combined with lenvatinib, with or without PD-1 inhibitors. Low PNI is associated with poor survival outcomes, highlighting its potential utility in risk stratification and treatment planning.