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Introduction: The benefits of neoadjuvant therapy (NAT) for pancreatic cancer (PC) with portal venous involvement remain debated. This study aimed to compare the short- and long-term outcomes of surgery with or without NAT in patients with PC with suspected venous involvement.

Methods: A multicentre retrospective cohort study compared patients who underwent upfront surgery (US) or surgery following NAT for PC with suspicion of venous involvement between 2007 and 2017. The primary endpoints were short-term morbidity and mortality, overall survival and disease-free survival.

Results: We included 361 patients who received NAT and 690 patients who underwent US at nine centres. NAT patients had greater suspicion of venous involvement (96.9% vs. 83.6%, p<0.001), but underwent fewer venous resections (53.7% vs. 79.3%, p<0.001), and had less venous infiltration (52.3% vs 65.9%, p<0.001), perineural invasion (75.2% vs. 90.1%, p<0.001), angioinvasion (59.9% vs. 76.7%, p<0.001), lymph node involvement (60.6% vs. 83.6%, p<0.001) and R1 resections (44.7% vs. 67.2%, p<0.001) than patients who underwent US. Among patients undergoing venous resection, major postoperative complications were similar between the groups. However, without venous resection, NAT patients had significantly fewer (Clavien-Dindo ≥IIIb) postoperative complications (10.8% vs. 24.4%, p=0.02), fewer reoperations (3.0% vs. 11.2%, p=0.006), and lower 90-day mortality (2.4% vs. 7.7%, p=0.03). NAT patients showed improved survival (27.3 vs. 21.2 months, p=0.003).

Conclusions: NAT maybe beneficial for patients with PC with venous involvement, as it might allow better patient selection for surgery and is associated with fewer major postoperative complications and better overall survival.