Redefining operability after neoadjuvant therapy in pancreatic ductal adenocarcinoma: a biology-driven surgical framework

Neoadjuvant therapy (NAT) has reshaped the management of pancreatic ductal adenocarcinoma (PDAC), improving systemic control and increasing margin-negative resection rates. However, it has also introduced complexity into surgical decision making. Post-treatment imaging, tumor markers, and pathologic findings frequently diverge, creating uncertainty regarding operability. Traditional anatomy-based frameworks are increasingly insufficient in the era of biologically driven therapy. The objective was to synthesize contemporary evidence and propose a practical, multidisciplinary framework for post-neoadjuvant surgical decision making in PDAC, particularly in the setting of discordant radiologic and biologic signals. A focused narrative review of PubMed-indexed literature (2015-2025) was conducted, emphasizing systematic reviews, prospective studies, and contemporary cohort analyses addressing response assessment, vascular resection, tumor regression grading, nodal downstaging, biomarker kinetics, and emerging technologies. Evidence was integrated into a structured tumor board–oriented decision framework. Post-NAT radiologic stability does not reliably indicate treatment failure, as therapy-induced fibrosis may mimic persistent vascular invasion. CA19-9 kinetics, staging laparoscopy, and patient physiologic reserve provide critical complementary information. Venous resection following NAT is oncologically justified in selected patients with favourable biology, whereas arterial resection requires stricter selection. Standardized pathology reporting, including tumor regression grading and nodal assessment, refines prognostication. Emerging tools such as circulating tumor DNA and radiomics show promise but require prospective validation. Post-neoadjuvant operability in PDAC demands integration of anatomy, biology, and patient resilience rather than reliance on a single modality. A structured, multidisciplinary framework enables biologically informed restraint or resection, ensuring that surgery is not merely technically feasible but oncologically justified.