A retrospective analysis of neoadjuvant chemotherapy (NAC) versus upfront surgery (US) in resectable pancreatic adenocarcinoma at a large tertiary care center.

e16448 Background: Resectable pancreatic adenocarcinoma (rPAC) has a notoriously high mortality worldwide, even in cases of complete resection. In previous decades, rPAC was treated with upfront surgical resection (US), however, neoadjuvant chemotherapy (NAC) is now recommended, especially for so-called high-risk cases, which are somewhat poorly characterized in both literature and guidelines. Many studies confirm that, for cases of borderline rPAC, NAC can reduce recurrence rates (RR), increase complete resection rates (R0), and increase overall survival (OS); however, the data remains conflicting for rPAC. Methods: This study aims to compare outcomes in rPAC with US versus NAC, comparing three primary endpoints: RR, R0, and OS. Initial analysis of all patients who underwent pancreatoduodenectomy between Jan 2020 - Dec 2024 was performed. Inclusion criteria included patients with pathology and imaging-proven rPAC. Exclusion criteria included patients with non-pancreatic adenocarcinoma or inconclusive biopsies, and all patients with borderline resectable tumors. A total of 27 patients were excluded, and a total of 56 patients were included. Key variables analyzed included patient demographics, tumor characteristics, R0, RR, and OS. Results: The US cohort (n=25) included 10 female and 15 male patients, with mean age at diagnosis 69.64 (SD 9.63) and mean tumor size 28.20mm (SD 10.38). The NAC cohort (n=31) included 16 female and 15 male patients, mean age at diagnosis was 72.23 (SD 9.51) and mean tumor size was 33.48mm (SD 13.46). There was no statistically significant difference in demographics or tumor size between cohorts. OS in the US cohort was 721.36 days; OS in the NAC cohort was 735.38 days. There was no statistically significant difference in overall survival between cohorts. In the US cohort, 23/25 patients achieved R0. In the NAC cohort, 23/31 patients achieved R0. Again, there was no statistically significant difference in R0 between cohorts. RR excluded patients with residual tumor after surgery, and this study found no statistically significant difference in RR between cohorts. Conclusions: This study found no statistically significant difference in outcomes between US and NAC for rPAC. Further randomized controlled trials (RCTs) are needed to fully evaluate the efficacy of NAC in rPAC, particularly high-risk rPAC. RCTs that examine the need for NAC, particularly in patients with high-risk features such as elevated Carbohydrate Antigen (CA) 19-9 levels and larger tumor size, would assist with the creation of less ambiguous evidence-based treatment guidelines. In the meantime, a multidisciplinary approach to treatment, as well as institutional guidelines for risk stratification, are critical.