Actual Five-year Survival After Neoadjuvant Therapy and Resection for Localized Pancreatic Ductal Adenocarcinoma

Objective: To determine actual 5-year survival after neoadjuvant therapy and resection for pancreatic ductal adenocarcinoma (PDAC). Background: Long-term outcomes after neoadjuvant therapy and resection for PDAC remain poorly defined, as current knowledge largely relies on actuarial estimates. Methods: Retrospective cohort study of consecutive patients who underwent neoadjuvant therapy followed by curative-intent pancreatectomy for localized PDAC at 2 high-volume centers between January 2015 and February 2021. Only patients with complete follow-up (death or ≥5 y) were included. The primary endpoint was actual 5-year survival from surgery. Results: Among 660 patients, actual 5-year survival was 34.5%. Recurrence occurred in 74.1% and was predominantly early, with nearly two-thirds of recurrences among patients who did not achieve 5-year survival occurring within 1 year after surgery. Long-term survivors had lower recurrence rates (92/228, 40.4%) and more commonly developed delayed (>2 y), locoregional, or pulmonary recurrence. The probability of achieving 5-year survival increased to 62.0% (95% CI: 56-67) and 81.9% (95% CI: 76-86) among patients who remained recurrence-free at 1 and 2 years, respectively. Actual 5-year survival was 42.5%, 29.0%, and 17.5% in patients with resectable, borderline-resectable, and locally advanced disease at diagnosis, respectively. Independent predictors of long-term survival included low comorbidity burden, baseline CA19-9 <200 U/mL, resectable disease at diagnosis, ypT0-1 stage, and R0 resection. Conclusions: Over one-third of patients undergoing neoadjuvant therapy and resection for localized PDAC were alive at 5 years, and most remained disease-free. Long-term outcomes were primarily determined by early systemic failure, whereas delayed oligometastatic recurrence identified a subgroup with prolonged survival.