Elevated Carcinoembryonic Antigen Levels Predict Failure to Reach Surgery in Patients with Borderline Resectable Pancreatic Cancer Referred to Neoadjuvant Therapy

Introduction: Neoadjuvant therapy (NT) is generally preferred over upfront surgery for borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC), but many patients fail to reach surgical resection. This study evaluates real-world outcomes of NT in BR-PDAC and identifies predictors of failure to proceed to surgery. Methods: A retrospective analysis of patients with resectable and BR-PDAC diagnosed between January 2015 and July 2024 was performed. Patient and disease characteristics were assessed to identify factors associated with NT dropout and failure to achieve surgical resection. Results: Of 161 BR-PDAC patients, 111 (69%) were referred to NT and 50 (31%) underwent upfront surgery. Among those referred to NT, 78 (70%) completed therapy and underwent resection. Reasons for failure to reach surgery included local tumor progression (39%), newly developed metastases (18%), and intraoperative findings (27%). Patients failing to reach surgery had significantly higher baseline bilirubin, white blood cell count, and carcinoembryonic antigen (CEA) levels. Elevated CEA significantly predicted surgical failure (adjusted odds ratio: 0.68 per 5-unit increase). Local progression was the primary cause of surgical failure in patients with elevated CEA (60%). Patients achieving resection had significantly improved overall survival (OS). There was no significant difference in OS or disease-free survival (DFS) between patients undergoing upfront surgery and those completing NT followed by resection. Conclusions: Elevated baseline CEA predicts failure to achieve surgical resection after NT, primarily owing to local progression. Multicenter studies are essential to refine patient selection criteria for upfront surgery and optimize personalized therapeutic strategies.