Abstract
BACKGROUND: Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are classical tumor markers in clinical practice. However, the relationship between tumor markers and prognosis in hepatocellular carcinoma (HCC) patients receiving immune checkpoint inhibitor (ICI) therapy remains unclear. OBJECTIVES: This study aims to explore the prognostic value of AFP and PIVKA-II in HCC patients treated with ICIs. DESIGN: This study was a single-center, retrospective investigation aimed to assess the prognostic value of AFP and PIVKA-II in HCC patients receiving immune checkpoint inhibitors. METHODS: This retrospective study included HCC patients who received ICIs treatment at Wuhan Union Hospital between July 2020 and March 2024. Serum AFP and PIVKA-II levels were collected before treatment. Patients were stratified into two groups based on AFP ⩾ 400 μg/L (yes = 1, no = 0) and PIVKA-II ⩾ 40 mAU/mL (yes = 1, no = 0). A total of 61% (114/186) of patients scored ⩽ 1, while 39% (72/186) scored 2. The objective response rate (ORR) and disease control rate (DCR) were calculated for both groups. Kaplan-Meier survival curves and Cox regression models were used to analyze overall survival (OS) and progression-free survival (PFS). Receiver operating characteristic curves were generated to demonstrate the predictive ability of combined independent prognostic factors for long-term survival. RESULTS: The cohort consisted of 186 patients, divided into the low-risk group (n = 114) and the high-risk group (n = 72). Among all patients, 34.4% (64/186) achieved complete or partial response. Concurrent elevation of AFP and PIVKA-II was inversely associated with ORR (p = 0.012). The high-risk group exhibited significantly shorter OS (adjusted HR: 2.226 (95% CI: 1.410-3.513); p < 0.001) compared to the low-risk group. The integrated model combining AFP, PIVKA-II, and Barcelona Clinic liver cancer stage demonstrated moderate to good predictive capability for long-term risk stratification, with time-dependent area under the curves of 0.78 (9-month), 0.68 (12-month), and 0.63 (15-month). CONCLUSION: Concurrent elevation of AFP and PIVKA-II is significantly associated with shorter survival outcomes in HCC patients following ICI therapy.