Survival Benefit of Surgery versus Oncology-Only Therapy in Artery-Involving Borderline Resectable and Locally Advanced Pancreatic Cancer

Background: Modern chemotherapy has redefined resectability of pancreatic ductal adenocarcinoma (PDAC), prioritizing tumor biology over anatomy. However, comparative outcomes of surgery versus continued oncologic therapy (COT) in borderline resectable (BR) or locally advanced (LA) PDAC remain unclear. This study addresses this gap. Patients and Methods: This retrospective, international, multicenter cohort study included patients with BR/LA-PDAC treated with neoadjuvant or primary chemotherapy between 2012 and 2024. All met guideline-based criteria for potential resection on the basis of anatomy, biology, and performance status. Treatment allocation (surgery versus COT) was based on institutional practice or surgeon preference, reflecting real-world decision-making. The primary endpoint was overall survival (OS), analyzed using unadjusted comparison, propensity score matching (PSM), and entropy balancing. Results: A total of 312 patients were included: 158 underwent resection and 154 received COT. Median OS was 39.0 months (IQR 14.3–42.6 months) with resection versus 16.7 months (IQR 8.8–22.5 months) with COT (p < 0.0001). After PSM (75 pairs), OS remained significantly longer with resection (42.6 months, IQR 12.9–42.1 months) versus COT (18.6 months, IQR 9.4–23.9 months; p < 0.0001). In the LA-PDAC subgroup, OS was 42.6 months (IQR 23.2–NA months) with resection versus 18.6 months (IQR 11.8–25.6 months; p < 0.0001) with COT. On multivariable analysis, resection (HR 0.34, 95% CI 0.21–0.54; p < 0.0001) and CA 19-9 (HR 1.0001; p = 0.0297) were independently associated with OS. Entropy-weighted models confirmed these findings. The survival benefit persisted when postoperative deaths were included. Conclusions: In patients with BR/LA-PDAC with favorable response to chemotherapy, surgical resection significantly improves survival compared with COT.