Pretreatment CA19‐9 Predicts Survival in Pancreatic Cancer With Optimal Response to Neoadjuvant Therapy

ABSTRACT Background and Objectives Pancreatic ductal adenocarcinoma (PDAC) is characterized by limited survival rates, yet patients who achieve optimal CA19‐9 response to neoadjuvant therapy (NAT) exhibit improved survival. This study examines the association between initial CA19‐9 levels and survival in PDAC patients who achieved CA19‐9 normalization with systemic chemotherapy. Methods A retrospective, multi‐institutional analysis of patients with resectable/borderline‐resectable PDAC, who underwent NAT and curative‐intent pancreatectomy at the University of Pittsburgh Medical Center, University of Texas Southwestern Medical Center, NorthShore University, and West Virginia University To contexualize thi between 2010 and 2022, was performed. CA19‐9 secretors (> 37 U/mL, with total bilirubin < 2) at diagnosis, with optimal response to NAT (normalization and > 50% drop in CA19‐9) were included. A cutoff for pre‐NAT CA19‐9 of 400 U/mL was determined to maximize sensitivity and specificity for survival benefit, and the cohort was accordingly divided into two groups. Kaplan–Meier and Cox proportional‐hazards models were used for univariate and multivariable analyses. Results A total of 134 patients were included, 32 (23.9%) had a pre‐NAT CA19‐9 ≥ 400U/mL. DFS and OS were considerably higher among patients with pre‐NAT CA19‐9 < 400U/mL (median(95%CI) in months, DFS:19.8(16.0,33.4) versus 7.8(5.0,13.0); OS:49.0(34.5,70.7) versus 23.1(13.8,50.9)). On multivariable analysis, pre‐NAT CA19‐9 ≥ 400 U/mL was significantly associated with reduced DFS and OS (DFS:HR = 2.4, p = 0.001; OS:HR = 1.9, p = 0.028). Conclusion In this select cohort of PDAC patients with optimal NAT response, pre‐NAT CA19‐9 ≥ 400U/mL is strongly associated with decreased DFS and OS.