Significance of Evaluating Tumor Markers in the Oncological Criteria for Resectability in Hepatocellular Carcinoma

ABSTRACT 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.