Cluster Analysis of HCC Prognosis Using Preoperative AFP and DCP Levels: A Multi-Institutional Study.

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, characterized by high recurrence rates post-curative resection. Tumor markers des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are crucial for HCC diagnosis and prognosis, yet their roles in the modern era of HCC epidemiology require reevaluation.

Methods: This multi-institutional retrospective study analyzed 1,515 patients who underwent hepatectomy for primary HCC. Patients were classified into four clusters using k-means analysis based on preoperative DCP and AFP levels. Clinicopathological characteristics, overall survival (OS), and recurrence rate (RR) were evaluated using Cox proportional hazards models and AUROC comparisons.

Results: Cluster 3 (concurrent elevations of DCP and AFP) had the poorest 5-year OS (52.8%) and highest RR (79.3%), while Cluster 4 (low levels of both markers) had the most favorable outcomes, with 5-year OS at 71.5% and RR at 55.7%. Cluster 1 (elevated DCP alone) was associated with larger tumors (median 45mm) and more frequent vascular invasion (43%) compared to Cluster 2 (elevated AFP alone, median tumor size 24mm, vascular invasion 36%). DCP was a stronger predictor of 5-year OS in patients with preserved liver function (AUROC 0.63), while AFP was more effective for stratifying RR in patients with impaired liver function (AUROC 0.57). NBNC-related HCC exhibited a distinct biomarker profile, with elevated DCP correlating with a higher 5-year RR (67%) compared to other etiologies.

Conclusion: This study introduces tumor marker clustering as a novel analytical approach, providing a nuanced understanding of AFP and DCP's combined utility in predicting prognosis and recurrence. These findings highlight the independent and complementary roles of these biomarkers, particularly in NBNC-related HCC and cases with impaired liver function. AFP and DCP remain critical tools for recurrence risk assessment, guiding personalized management strategies such as surveillance, neoadjuvant therapies, and tailored postoperative interventions.