Annals of surgical oncology · 2026
Assessing Response and Outcomes to Modern Multiagent Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma.
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McClelland Paul H, Satyadi Megan A, Johnson Ryan P, Jacob Rosetta, Pan Jianmin, Rai Jayesh, Rai Shesh, Sohal Davendra, Olowokure Olugbenga, Kharofa Jordan, Wilson Gregory C, Patel Sameer H, Ahmad Syed A
Аннотация
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.
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.