Preoperative tumor marker burden score predicts survival in colorectal cancer according to tumor size

BACKGROUND: Reliable preoperative biomarkers are needed to improve risk stratification in colorectal cancer (CRC). The prognostic value of a combined score based on multiple serum tumor markers remains underexplored. METHODS: This retrospective study included 307 CRC patients undergoing curative surgery. A preoperative risk score was defined by the number of elevated markers (AFP, CA19-9, CA125, CA724, CA153) above institutional cut-offs. Patients were stratified into low-risk (≤ 1 elevated marker) and high-risk (> 1 elevated marker) groups. Associations with 5-year disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression. Subgroup analysis by tumor size (≤ 4 cm vs. >4 cm) was performed. RESULTS: A low-risk score (≤ 1 elevated marker) was independently associated with improved 5-year OS (adjusted HR = 0.60, 95% CI: 0.37-0.97, P = 0.038) and showed a strong trend for better DFS (adjusted HR = 0.65, 95% CI: 0.42-1.00, P = 0.051) after adjusting for clinicopathological factors. Strikingly, this prognostic association was significant only in patients with tumors ≤ 4 cm (for OS: HR = 0.19, P = 0.003; for DFS: HR = 0.34, P = 0.010) but not in those with larger tumors (P > 0.05). The interaction between tumor size and the marker score on OS approached statistical significance (P for interaction = 0.051). CONCLUSION: A simple preoperative multi-marker score is an independent prognostic factor for survival in CRC. Its predictive power is particularly strong in patients with smaller tumors (≤ 4 cm), suggesting a valuable role in refining preoperative risk assessment for this subgroup.