Simple SummaryIn this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors and 149 long-term survivors and compared them to 352 intermediate-term survivors of pancreatic ductal adenocarcinoma (PDAC) who received NAT and pancreatoduodenectomy. We found that lymph node stage (ypN) was an independent predictor of both short-term and long-term survivors. In addition, tumor differentiation was an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.AbstractNeoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15–60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p= 0.03), tumor resectability prior to NAT (p= 0.04), poorly differentiated tumor histology (p= 0.006), more positive lymph nodes (p= 0.04), higher ypN stage (p= 0.002), and higher positive lymph node ratio (p= 0.03). The long-term survivor group had smaller tumor size (p= 0.001), lower ypT stage (p= 0.001), fewer positive lymph nodes (p< 0.001), lower ypN stage (p< 0.001), lower positive lymph node ratio (p< 0.001), lower rate of lymphovascular invasion (p= 0.001) and perineural invasion (p< 0.001), better tumor response grading (p< 0.001), and less frequent recurrence/metastasis (p< 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.