Simple SummaryIn this paper, we showed that only a minority of patients (23%) undergoing upfront pancreatic resection completed the planned 12 courses of FOLFIRINOX, and we delineated the reasons for not completing it. We showed that patients who received neoadjuvant treatment were significantly more likely to receive six treatment courses, and that those who received at least six courses had better overall survival than those who did not. We suggest considering the potential ways of increasing chemotherapy adherence, such as administering treatment before surgery. We believe this article will promote research that has already started—neoadjuvant treatment for patients with resectable pancreatic cancer.AbstractBackground: The recommended treatment for resectable pancreatic cancer (PC) is resection followed by adjuvant FOLFIRINOX. We assessed the proportion of patients that managed to complete the 12 courses of adjuvant FOLFIRINOX and compared their outcome with that of patients with borderline resectable pancreatic cancer (BRPC) who underwent resection after neoadjuvant FOLFIRINOX. Methods: A retrospective analysis was performed on a prospectively maintained database of all PC patients who underwent resection with (2/2015–12/2021) or without (1/2018–12/2021) neoadjuvant therapy. Results: A total of 100 patients underwent upfront resection, and 51 patients with BRPC received neoadjuvant treatment. Only 46 resection patients started adjuvant FOLFIRINOX, and only 23 completed 12 courses. The main reasons for not starting/completing adjuvant therapy were poor tolerance and rapid recurrence. Significantly more patients in the neoadjuvant group received at least six FOLFIRINOX courses (80.4% vs. 31%,p< 0.001). Patients who completed at least 6 courses, either pre- or postoperatively, had better overall survival (p= 0.025) than those who did not. In spite of having more advanced disease, the neoadjuvant group had comparable overall survival (p= 0.062) regardless of the number of treatment courses. Conclusion: Only a minority of patients (23%) undergoing upfront pancreatic resection completed the planned 12 courses of FOLFIRINOX. Patients who received neoadjuvant treatment were significantly more likely to receive at least six treatment courses. Patients receiving at least six courses had better overall survival than those who received fewer than six courses, regardless of the timing of treatment relative to surgery. Potential ways to increase chemotherapy adherence, such as administering treatment before surgery, should be considered.