Tumor Burden Score and Alpha-Fetoprotein Level Predict Prognosis of Patients with Unresectable Hepatocellular Carcinoma Treated with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody

Tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies in combination provide survival benefits for patients with unresectable hepatocellular carcinoma (uHCC). However, the tool used to determine which patients likely benefit most from this treatment strategy has not been reported. We sought to develop a prognostic scoring system based on tumor burden score (TBS) and alpha-fetoprotein (AFP) to predict the long-term prognosis of uHCC treated with TKIs and anti-PD-1 antibodies. Data on patients with uHCC treated with TKIs and anti-PD-1 antibodies from multiple centers were collected. The prognostic accuracy of TBS, AFP, Barcelona Clinic Liver Cancer (BCLC), and CTA (Combined TBS and AFP) for 2-year progression-free survival (PFS) and overall survival (OS) was evaluated. Overall, 278 patients with uHCC treated with TKIs and anti-PD-1 antibodies were enrolled, including 48 BCLC-B and 230 BCLC-C HCC patients. CTA (AUC = 0.721 and 0.683) outperformed TBS (AUC = 0.680 and 0.621), AFP (AUC = 0.606 and 0.594), and BCLC staging (AUC = 0.551 and 0.555) in predicting PFS and OS. The 2-year PFS and OS for low CTA (low TBS/low AFP) were 65.7% and 94.4%, respectively, which were significantly higher than 21.6% and 44.9% (p < 0.001 and p = 0.002), respectively, for intermediate CTA (low TBS/high AFP or high TBS/low AFP) and 8.7% and 12.1% (both p < 0.001), respectively, for high CTA (high TBS/high AFP). Multivariable Cox regression analysis indicated that CTA grading was an independent prognostic factor for PFS and OS (referent: low CTA; intermediate CTA, HR 2.87 and 7.17; high CTA, HR 5.52 and 10.31, respectively). CTA grading is an accurate tool for stratifying the prognosis of uHCC treated with TKIs and anti-PD-1 antibodies and may help determine which patients may benefit more from this treatment strategy.