Neoadjuvant Chemotherapy for Intraductal Papillary Mucinous Neoplasm-derived Pancreatic Cancer

Summary of Background Data: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is typically managed like pancreatic intraepithelial neoplasia (PanIN)-derived pancreatic cancer. However, in IPMN-derived pancreatic cancer, the role of chemotherapy remains controversial, particularly in the neoadjuvant setting (NAT). Objective: To evaluate the role of neoadjuvant chemotherapy in IPMN-derived pancreatic cancer. Methods: Patients with IPMN-derived pancreatic cancer treated with either upfront surgery (US) or NAT were identified from eight international centers (2000-2023). Clinicopathologic data were compared. Date of first treatment was used for Kaplan-Meier and log-rank tests to compare overall (OS) and recurrence free survival (RFS). Multivariable Cox-regression was performed in patients that underwent NAT. Results: In 1,019 patients, 76 (7%) underwent NAT. Patients who received NAT had higher baseline CA19-9 levels ( P <0.001). Of these 76 patients, 27 (36%), 20 (26%), and 29 (38%) had resectable, borderline resectable, or locally advanced pancreatic cancer at diagnosis, respectively. Advanced resectability stage was significantly more common in the NAT patients as compared to those who underwent US ( P <0.001). OS for US patients was 38.0 months (95%CI: 33.7.1-44.3), which was not statistically different than those that received NAT [27.5 mo (95%CI: 23.1-46.7), P =0.121]. This was also valid for patients with resectable disease [US: 38.1 mo vs. NAT: 35.6 mo, P =0.920)]. Complete or marked pathological treatment response ( P =0.046) and serological CA19-9 normalization after NAT ( P =0.017) were associated with improved survival. On Cox-regression for OS, N2 disease [HR: 4.15 (95%CI: 1.71-10.10)], elevated CA19-9 [HR: 2.02 (95%CI:1.06-3.85)] and R1 margin [HR: 2.36 (95%CI:1.20-4.61)] was independently associated with OS after NAT, while resectability status was not. Conclusion: After NAT and resection, advanced resectability stage was not associated with worse OS indicating the value of this approach for borderline resectable and locally advanced IPMN-derived pancreatic cancer. The benefit of NAT in resectable disease is unclear and may require an individualized approach. Biological treatment effect can be assessed with CA19-9 and confirmed by pathologic response.