Predictors of short- and long-term survival in unresectable hepatocellular carcinoma (uHCC) treated with transcatheter arterial chemoembolization combined with lenvatinib plus PD-1 inhibitors: a multicenter retrospective study

<h2>Abstract</h2><h3>Background</h3> Transcatheter arterial chemoembolization combined with lenvatinib plus PD-1 inhibitors (triple therapy) is a promising treatment modality for uHCC. Identifying variables influencing prognosis can facilitate more personalized treatment. This study aimed to determine predictors of short-term survival (STS) and long-term survival (LTS) in patients with uHCC treated with triple therapy. <h3>Methods</h3> This multicenter retrospective study reviewed patients with uHCC who underwent triple therapy at seven tertiary hospitals in China between June 2018 and May 2023. STS was defined as survival <12 months from the initiation of treatment, and LTS was defined as survival ≥24 months. Univariate and multivariate logistic regression analyses were performed to identify predictors of STS and LTS. Variables examined were: age, gender, hepatitis B virus infection, performance status, alpha-fetoprotein, macrovascular invasion, extrahepatic metastasis, tumor size, tumor number, total bilirubin, albumin, alanine aminotransferase, aspartate transaminase, and albumin-bilirubin grade. <h3>Findings</h3> 289 patients were included, with the following baseline characteristics: median age 55.7 years, 88.2% male, 87.2% hepatitis B virus infection, 26.3% Barcelona Clinic Liver Cancer stage B, and 73.7% stage C. Treatment-related adverse events occurred in 88.2% of patients, with 29.8% experiencing grade 3–5 adverse events. Median overall survival was 29.2 months (95% confidence interval, 23.1–NA). Sixty-five (22.5%) patients had STS and 89 (30.8%) had LTS. The independent predictors of STS were alpha-fetoprotein level ≥400 ng/mL [odds ratio (OR), 2.04; p=0.033], extrahepatic metastasis (OR, 3.83; p < 0.001), and maximum tumor size ≥5 cm (OR, 3.79; p=0.039). Absence of macrovascular invasion (OR, 1.99; p=0.019), absence of extrahepatic metastasis (OR, 3.01; p=0.008), and maximum tumor size <5 cm (OR, 2.85; p=0.002) were independent predictors of LTS. <h3>Interpretation</h3> Higher alpha-fetoprotein levels, extrahepatic metastasis, and larger tumor size were predictors of STS, while no macrovascular invasion, no extrahepatic metastasis, and smaller tumor size predicted LTS in patients with uHCC treated with triple therapy. These findings may help guide treatment decisions in uHCC. <h3>Funding</h3> This study was funded by the Medical Innovation Project of Health and Family Planning Commission of Fujian Province (Grant number: 2022CXA002).