The Concept of Biological Resectability in Pancreatic Ductal Adenocarcinoma - An Updated Narrative Review

Resectability in pancreatic ductal adenocarcinoma (PDAC) has traditionally been defined according to tumor-vessel relationship on cross-sectional imaging. However, anatomical criteria alone fail to identify occult systemic disease and do not reliably predict early postoperative recurrence or the likelihood of meaningful oncological benefit from surgery. This structured narrative review evaluated contemporary evidence regarding biological resectability and the emerging role of biomarkers in perioperative decision-making. A literature search was conducted using PubMed/MEDLINE, Embase, and Web of Science, focusing on studies published between January 2017 and March 2026, with inclusion of seminal earlier publications where relevant. Priority was given to consensus statements, clinical practice guidelines, meta-analyses, randomized controlled trials, prospective cohort studies, and large multicentre series. Evidence was qualitatively synthesized and biomarkers were classified according to their level of clinical maturity. Emerging data suggest that many anatomically resectable PDACs exhibit biologically aggressive disease associated with occult metastases, early recurrence, and limited benefit from upfront surgery. Among available biomarkers, carbohydrate antigen 19-9 remains the most clinically established and should be interpreted in the context of biliary status, treatment response, and multidisciplinary assessment. Circulating tumor DNA shows promise for molecular staging and recurrence risk stratification, although prospective interventional validation remains limited. Transcriptomic subtypes, positron emission tomography (PET)-derived biomarkers, radiomics, and hybrid multimodal models provide additional biological insights but remain largely investigational. Biological resectability is increasingly recognized as an important complement to anatomical staging, helping to refine patient selection and treatment sequencing. Nevertheless, prospective validation, assay standardization, and biomarker-guided clinical trials are required before widespread implementation in routine multidisciplinary practice.