Perioperative prognostic factors of early recurrence in resectable pancreatic ductal adenocarcinoma following neoadjuvant chemotherapy: A retrospective multicenter study

Background Neoadjuvant chemotherapy (NAC) has been increasingly adopted to improve oncological outcomes in patients with resectable pancreatic ductal adenocarcinoma (R-PDAC); however, early recurrence after curative resection remains frequent. This study examined potential perioperative prognostic factors of recurrence within 2 years after resection in patients with R-PDAC treated with NAC. Methods This multicenter retrospective study analyzed 100 consecutive patients with R-PDAC who underwent radical resection following NAC with gemcitabine plus S-1 between 2019 and 2023. Patients were categorized according to recurrence-free survival (RFS; <2 years vs. ≥2 years). Multivariate logistic regression analysis was performed to identify independent prognostic factors of early recurrence. Results Early recurrence occurred in 45.0% of patients. Multivariate analysis identified five independent prognostic factors of early recurrence: pre-NAC carbohydrate antigen 19 − 9 (CA19-9) ≥ 75 U/mL, post-NAC tumor size ≥ 17 mm, post-NAC CA19-9 > 37 U/mL, pathological tumor size ≥ 22 mm, and pathological lymph node metastasis (pN1). Among factors available prior to surgery, a risk stratification model incorporating pre-NAC CA19-9 levels, post-NAC tumor size, and post-NAC CA19-9 levels was effectively associated with RFS. Two-year RFS rates decreased stepwise according to the number of prognostic factors (0, 76.7%; 1, 62.3%; ≥2, 31.4%; p  < 0.01). Conclusions Early recurrence after NAC in R-PDAC is driven by both aggressive tumor biology and insufficient radiological response. Perioperative risk stratification might help inform individualized neoadjuvant strategies, including treatment intensification in high-risk patients.