Duke Pancreatic Monoclonal Antigen Type 2 for Monitoring Carbohydrate Antigen 19-9 Nonexpressor Pancreatic Cancer.

Abstract

Approximately 5% to 10% of patients with pancreatic cancer are carbohydrate antigen 19-9 (CA 19-9) nonexpressors (≤2 U/mL), predominantly due to the Lewis-negative phenotype, leaving them without established biomarkers for treatment monitoring despite the central role of biomarker assessment in modern pancreatic cancer management. To evaluate Duke pancreatic monoclonal antigen type 2 (DUPAN-2) as a surrogate biomarker for monitoring treatment response in patients with CA 19-9 nonexpressor pancreatic cancer. This cohort study included patients with resected pancreatic ductal adenocarcinoma from 9 Japanese academic centers between January 1, 2013, and December 31, 2019. Patients were classified as CA 19-9 nonexpressors (≤2 U/mL) or expressors (>2 U/mL). Median (IQR) follow-up was 55.3 (38.5-74.1) months for expressors and 51.1 (39.3-72.4) months for nonexpressors. Two analysis cohorts were defined among nonexpressors: those with postneoadjuvant DUPAN-2 measurements and those with postresection DUPAN-2 measurements. Data were analyzed from July 2024 to February 2026. DUPAN-2 levels after neoadjuvant therapy and after resection, with normal levels defined as ≤150 U/mL. Overall survival (OS) and disease-free survival (DFS) calculated from the date of resection. Among 2418 patients (median [IQR] age, 70 [63-76] years; 1404 [58.1%] male), 185 (7.7%) were CA 19-9 nonexpressors and 2233 (92.3%) were expressors. Nonexpressors and expressors showed comparable OS (adjusted hazard ratio [HR], 1.10; 95% CI, 0.89-1.37). DUPAN-2 dynamics in nonexpressors mirrored CA 19-9 patterns in expressors, with comparable median (IQR) reductions (postneoadjuvant: -64.5% [-82.2 to -37.2] vs -67.1% [-89.0 to -25.9]; postresection: -71.4% [-84.4 to -48.8] vs -73.4% [-90.7 to -35.4]). Achieving normal DUPAN-2 levels (≤150 U/mL) after neoadjuvant therapy was associated with improved OS (adjusted HR, 0.26; 95% CI, 0.07-0.93) and DFS (adjusted HR, 0.15; 95% CI, 0.04-0.53). Similarly, normal postresection DUPAN-2 was associated with better OS (adjusted HR, 0.18; 95% CI, 0.06-0.55) and DFS (adjusted HR, 0.23; 95% CI, 0.08-0.64). In this cohort study, DUPAN-2 served as an effective surrogate biomarker for patients with CA 19-9 nonexpressor pancreatic cancer, with normal posttreatment levels associated with favorable outcomes. These findings suggest that routine DUPAN-2 monitoring may enable biomarker-guided treatment decisions for this previously unassessable subgroup.