What question did this study set out to answer?

To evaluate the effectiveness of multiagent neoadjuvant therapy in treating pancreatic ductal adenocarcinoma and its relation to survival outcomes.

June 20, 2026Open Access

Assessing Response and Outcomes to Modern Multiagent Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma

PMPaul H. McClellandUniversity of Cincinnati MSM. SatyadiOncology Hematology Care RJRyan P. JohnsonUniversity of Cincinnati

Key Points

To evaluate the effectiveness of multiagent neoadjuvant therapy in treating pancreatic ductal adenocarcinoma and its relation to survival outcomes.
Single-center retrospective review of patients with resectable or borderline-resectable pancreatic ductal adenocarcinoma treated with neoadjuvant therapy from 2008 to 2024.
Assessment of radiographic response using RECIST 1.1, biochemical response through CA 19-9 reduction, and histopathologic response via CAP score.
Analysis of overall survival and progression-free survival as primary and secondary outcomes.
148 out of 166 patients (89%) completed neoadjuvant therapy; 121 patients (73%) underwent resection.
27% of patients showed tumor regression post-therapy, while 83% had significant CA 19-9 reduction; 74% of resected patients had histopathologic response.
Histopathologic response (CAP 0-2) was linked to improved PFS (adjusted HR 0.57, 95% CI 0.34-0.96; p=0.034), unlike radiographic or biochemical responses which did not significantly improve survival.

Abstract

Abstract Background Neoadjuvant therapy (NAT) is increasingly used for resectable and borderline-resectable pancreatic ductal adenocarcinoma (PDAC), yet interpretation of treatment response remains challenging. Patients and Methods A single-center retrospective review was conducted of patients with resectable or borderline-resectable PDAC treated with multiagent NAT between 2008 and 2024. Radiographic response was assessed using RECIST 1.1 criteria, biochemical response by serum CA 19-9 reduction, and histopathologic response by College of American Pathologists (CAP) score. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Results Among 166 patients, 148 (89%) completed NAT and 121 (73%) underwent resection. After NAT, radiographic response was uncommon: 27% had tumor regression, 66% stable disease, and 7% progressive disease. By contrast, 83% achieved ≥ 45% CA 19-9 reduction after NAT, and 74% demonstrated histopathologic response after resection, including 8% complete pathologic response. Among resected patients with radiographically stable/progressive disease, 88% had biochemical response and 68% at least partial histopathologic response. Neither radiographic nor biochemical response were significantly associated with improved PFS or OS. Histopathologic response (CAP 0–2) was associated with improved PFS/OS on univariable analysis as well as improved PFS on multivariable analysis adjusted hazard ratio (aHR) 0.57, 95% confidence interval (CI) 0.34–0.96; p = 0.034. Isolated unresectable local progression during NAT was rare ( n = 2). Conclusions While imaging response and downstaging can occur with NAT, histopathologic response is more predictive of long-term survival and often occurs despite stable or progressive disease on imaging. Isolated unresectable local progression after NAT is rare, though broader treatment-related attrition remains a consideration in neoadjuvant sequencing.

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