Clinical Outcomes of AFP-Negative Patients with Advanced HCC: A Propensity-Matched Analysis from a Retrospective...

Area of Science:

• Hepatocellular Carcinoma Research
• Medical Oncology
• Biomarker Analysis

Background:

• Alpha-fetoprotein (AFP) positivity (≥20 ng/mL) is a common diagnostic criterion for hepatocellular carcinoma (HCC).
• The prognostic implications of negative AFP levels (<20 ng/mL) in advanced HCC following systemic therapy remain underexplored.

Purpose of the Study:

• To analyze the prognosis of advanced HCC patients with negative baseline AFP levels compared to those with positive AFP levels.
• To evaluate the efficacy of different systemic drug treatments in AFP-negative advanced HCC.

Main Methods:

• Retrospective analysis of 91 AFP-negative and 213 AFP-positive advanced HCC patients treated from February 2011 to September 2023.
• Propensity score matching (1:2 ratio) was employed to create comparable groups (90 AFP-negative vs. 180 AFP-positive).
• Cox regression analysis was utilized to assess prognostic differences and treatment efficacy.

Main Results:

• AFP-negative advanced HCC patients demonstrated a significantly longer overall survival (OS) by 13.5 months compared to AFP-positive patients.
• In AFP-negative HCC, first-line treatment with tyrosine kinase inhibitors (TKIs) combined with immune checkpoint inhibitors (ICIs) yielded the best outcomes (mPFS = 9.5m, mOS = 37.1m).
• Patients without portal vein tumor thrombus (PVTT) or with HBV DNA <50 IU/mL showed improved survival and treatment efficacy.

Conclusions:

• Advanced HCC with negative AFP is associated with a better prognosis than AFP-positive HCC.
• First-line therapy with TKIs plus ICIs, followed by TKIs alone for second-line treatment, is recommended for AFP-negative advanced HCC.
• Systemic drug therapy efficacy is enhanced in AFP-negative HCC patients without PVTT or with low HBV DNA levels.