Upfront surgery versus neoadjuvant chemotherapy in resectable pancreatic adenocarcinoma.

e16472 Background: There is no clear consensus regarding treatment sequence for resectable pancreatic ductal adenocarcinoma (PDAC). Upfront resection followed by adjuvant chemotherapy and neoadjuvant therapy are two acceptable treatment options. We compared outcomes of upfront surgery followed by adjuvant chemotherapy versus neoadjuvant chemotherapy followed by surgery using retrospectively collected data at our stand-alone cancer center. Methods: We analyzed a total of 240 resectable patients with PDAC who were retrospectively enrolled in an institutional REDCap database from 2017-2024. After excluding patients who underwent palliation (n = 34) and those whose surgeries were performed outside the institution (n = 13), 193 patients were included. Patients were categorized into two groups: upfront resection (UR, n = 91) and neoadjuvant chemotherapy followed by resection (NAC, n = 102). Clinicopathologic variables, perioperative outcomes, and overall survival were compared. Kaplan–Meier survival analysis and Cox proportional hazards modeling were used to evaluate survival differences and identify independent prognostic factors. Results: 193 patients were included in the study. 91 (47.2%) underwent upfront resection and 102 (52.8%) were treated with neoadjuvant chemotherapy. Median overall survival was 38.8 months in the upfront resection population versus 22.5 months for patients in the neoadjuvant cohort (log-rank p = 0.064). On multivariate Cox proportional hazards analysis for overall survival, higher baseline CA19-9 (HR 1.047, 95% CI 1.004-1.092; p = 0.033) and greater Charlson-Deyo comorbidity burden (p = 0.030) were independently associated with worse survival whereas association with treatment sequence was not statistically significant (p = 0.087). In the neoadjuvant cohort, 31 patients (30.4%) did not undergo surgical resection due to disease progression, decline in performance status, patient refusal, or loss to follow-up. Conclusions: In patients with resectable PDAC at a stand-alone cancer center, both upfront surgery and neoadjuvant chemotherapy are acceptable treatment options. Evaluation of early recurrence in a subgroup of patients receiving upfront surgery suggests more careful consideration of treatment sequence may benefit outcomes. Attrition in the neoadjuvant cohort suggests potential opportunities to improve selection or implement targeted interventions to facilitate patient navigation through complex multidisciplinary therapy. Multivariate cox models - overall survival. Multivariate Cox Models - Overall Survival HR 2.50% 97.50% Overall P-Value Charlson-Deyo Comorbidity Total Score 1 0.7141 0.4386 1.163 0.02965 2-3 1.573 0.9868 2.506 4+ 1.605 0.5621 4.585 Baseline CA19-9 1.047 1.004 1.0924 0.03266