Impact of Dynamic Changes in Multiple Serum Tumor Markers During Neoadjuvant Therapy on Clinical Outcome in Gastrointestinal Cancer.

Background: Dynamic shifts in serum tumor markers during neoadjuvant therapy could refine prognostication in gastrointestinal (GI) cancers, but supporting evidence is limited.

Methods: We prospectively followed 200 patients with gastric (55%) or colorectal (45%) cancer who received neoadjuvant chemotherapy ± radiotherapy and curative-intent surgery (2016-2025). Carcinoembryonic antigen (CEA), CA19-9, CA72-4 and CA125 were assayed at baseline and pre-surgery. Three-year disease-free survival (DFS) and overall survival (OS) were primary endpoints. Multivariable Cox models assessed associations between marker dynamics and outcomes.

Results: Baseline positivity rates were 40% for CEA and 30% for CA19-9; 31% of patients had ≥ 2 markers elevated. Therapy converted 45% of CEA-positive and 53% of CA19-9-positive cases to negative. Major pathological response (Tumor Regression Grade 0-1) occurred in 30% overall and was higher in marker converters than non-converters (45% vs 18%, p < 0.001). Persistent positivity correlated with lower R0 resection (78% vs 91%, p = 0.04), more complications (26% vs 12%, p = 0.03) and poorer 3-year DFS (42% vs 69%). On multivariable analysis, persistence of ≥ 2 positive markers independently predicted shorter DFS (HR 1.9, 95% CI 1.2-3.0) and OS (HR 2.1, 95% CI 1.3-3.3). Sensitivity analyses using alternative cut-offs, multiple imputation and exclusion of borderline metastatic cases yielded consistent results.

Conclusion: Failure of serum tumor markers to normalize after neoadjuvant therapy signals inferior pathological response and survival. Serial marker assessment can enhance perioperative risk stratification and guide surgical decisions in GI cancers.