Background: The Japan Liver Cancer Association and the Japanese Society of Hepato-Biliary-Pancreatic Surgery proposed oncological resectability criteria for hepatocellular carcinoma (HCC), classifying tumors as R, BR1, or BR2. However, serum tumor markers, such as alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP), despite their prognostic value, were not incorporated.
Methods: We retrospectively analyzed 803 patients undergoing curative liver resection for HCC. Significant tumor marker elevation (TM-high) was defined as AFP > 500 ng/mL or DCP > 1000 mAU/mL. Overall survival (OS) and relapse-free survival (RFS) were compared according to resectability status and tumor marker levels.
Results: TM-high status was observed in 171 patients with R (32.3%), 75 patients with BR1 (27.5%), and 46 patients with BR2 (70.1%). In the R group, TM-high patients had significantly worse outcomes than non-TM-high patients (median survival time [MST], RFS: 26.9 vs. 55.9 months, and p < 0.001; OS: 120.7 vs. 160.8 months and p = 0.008). No significant difference in the OS was observed between R/TM-high and BR1/non-TM-high patients (120.7 vs. 103.1 months and p = 0.159) or BR1/TM-high and BR2/non-TM-high patients (58.7 vs. 58.5 months and p = 0.657). Multivariate analyses confirmed that a TM-high status was an independent predictor for both the RFS (HR 1.36 and p < 0.003) and OS (HR 1.50 and p < 0.001).
Conclusion: AFP and DCP provide independent prognostic information beyond the oncological resectability criteria. Incorporating tumor markers may refine risk stratification and optimize multidisciplinary treatment strategies for HCC.
Keywords: alpha‐fetoprotein; des‐gamma‐carboxyprothrombin; hepatocellular carcinoma; oncological resectability criteria; resectability; tumor makers.
© 2025 Japan Society of Hepatology.