Survival Outcomes in Patients with Advanced Hepatocellular Carcinoma Based on Pretreatment Serum Lactate Dehydrogenase Level and Albumin-Bilirubin Grade: A Single-Center, Retrospective, Non-Randomized Cohort Study.

Abstract

Background: Hepatocellular carcinoma (HCC) is a major global contributor to cancer mortality. The primary objective of this study was to compare the prognostic value of pretreatment albumin-bilirubin (ALBI) grade and serum lactate dehydrogenase (LDH) levels in patients with advanced hepatocellular carcinoma receiving first-line triple therapy consisting of immune checkpoint inhibitors (ICI), targeted agents, and radiotherapy.

Methods: This single-center retrospective cohort study enrolled 143 unresectable advanced HCC patients treated with ICI-targeted combined radiotherapy from 2019 to 2023. Patients were stratified by baseline ALBI grade (1 vs 2) and LDH levels (LDH-0: ≤ 250 U/L vs LDH-1: > 250 U/L). Treatment response was evaluated per mRECIST 1.1, and adverse events (AEs) were graded by NCI-CTCAE v4.0. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety profiles. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the standalone predictive performance of ALBI grade and LDH status for OS and PFS endpoints.

Results: ALBI-1 and LDH-0 patients obtained significantly higher ORR and DCR than ALBI-2 and LDH-1 patients (P < 0.05 and P < 0.001, respectively). No efficacy gaps existed between favorable-risk subgroups (ALBI-1 vs LDH-0) or poor-risk subgroups (ALBI-2 vs LDH-1). The cohort's median OS and PFS were 15.7 and 12.8 months. Univariate analysis showed ALBI-1 was associated with lowered risks of death (Hazard ratio (HR) = 0.27, P < 0.001) and progression (HR = 0.38, P < 0.001), although this association was not statistically significant in multivariate Cox models, while LDH-0 reduced mortality (HR = 0.33, P < 0.001) and progression risks (HR = 0.53, P = 0.007). ALBI-1 and LDH-0 had comparable survival, and LDH-1 patients showed numerically better survival than ALBI-2 patients. ROC curves showed weak predictive ability for single ALBI or LDH (all areas under the curves near 0.5). ALBI-2 patients suffered more grade 1-4 AEs, whereas LDH subgroups showed no consistent toxicity differences.

Conclusions: Pretreatment ALBI grade and LDH showed comparable prognostic stratification performance for advanced HCC receiving triple therapy, while ALBI grade better predicts treatment-related toxicities. Single markers had limited predictive efficacy, and combined ALBI-LDH scoring may improve clinical risk stratification, although its added clinical value requires prospective external validation.