Efficacy of Neoadjuvant Therapy and the Prognostic Significance of Serum Carcinoembryonic Antigen Level in Patients with Localized Pancreatic Adenocarcinoma with Non-elevated Carbohydrate Antigen 19-9 Levels

Abstract

Objective: This study evaluated the effect of neoadjuvant therapy (NAT) and the prognostic significance of carcinoembryonic antigen (CEA) levels in patients with non-elevated serum carbohydrate antigen (CA) 19-9 levels.

Summary background data: The impact of NAT followed by surgical resection on oncologic outcomes in patients with localized pancreatic ductal adenocarcinoma (PDAC) remains unclear.

Methods: This retrospective and propensity-score matched (PSM) study included primary and validation cohorts from four centers. Propensity scores were estimated using multivariable logistic regression and survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. overall survival (OS) and recurrence-free survival (RFS) were compared and univariable and multivariable Cox proportional hazards regression model were applied.

Results: Among 251 patients with PDAC with non-elevated CA 19-9 levels, 67 received NAT followed by surgical resection, and 184 underwent upfront surgery. Following PSM, NAT significantly improved OS (39.87 vs. 18.86 months, P=0.0175) and RFS (25.67 vs. 12.83 months, P=0.0197) compared to upfront surgery. These results validated in an independent external cohort. In the primary cohort after PSM, elevated CEA was associated with worse OS and RFS compared to non-elevated CEA (median OS: 18.86 months vs. 42.39 months, P=0.0014, and median RFS: 17.40 months vs. 28.60 months, P=0.0020). Furthermore, after adjusting for competing risk factors, elevated CEA was identified as an independent factor associated with both OS (hazard ratio (HR): 1.751, 95%CI: 1.087-2.821; P=0.021) and RFS (HR: 1.637, 95%CI: 1.046-2.561; P=0.031). These results were validated in an independent external cohort.

Conclusion: NAT followed by surgical resection improves outcomes in patients with PDAC with non-elevated CA 19-9 levels. Elevated CEA levels were associated with adverse prognostic effects on both OS and RFS. These findings support the need for further evaluation of patients with non-elevated CA 19-9 levels and serum CEA levels in prospective settings.

Keywords: CA 19-9; CEA level; Neoadjuvant Therapy.