A Neoadjuvant Therapy Compatible Prognostic Staging for Resected Pancreatic Ductal Adenocarcinoma

Abstract Objective: A refined staging system compatible with upfront surgery (UFS) and neoadjuvant therapy (NAT) for PDAC was developed to revise the prediction ability of the AJCC staging system. Background: The AJCC staging system was developed for patients who have undergone UFS for PDAC, and it has limited prognostic ability for patients receiving NAT. Methods: We analyzed 146 PDAC patients who underwent resection after NAT and 1771 patients who underwent UFS between 2012 and 2021 at the Changhai Hospital. Cox proportional regression analysis was used to identify the clinicopathological features and the Neoadjuvant Therapy Compatible Prognostic (NATCP) staging was designed based on these variables. Validation was performed in the prospective NAT cohort and the SEER database. The staging system was then compared with the AJCC staging system in terms of prognostic accuracy. Results: The multivariate analysis demonstrated that tumor differentiation and number of positive lymph nodes were independently associated with OS in the NAT cohort. The NATCP staging simplified the AJCC stages, incorporated tumor differentiation and restaged the disease according to the survival differences observed in the Kaplan-Meier curves. The median OS for NATCP stages IA, IB, II and III were not reached, 31.7 months, 25.0 months, 15.8 months in the NAT cohort and 30.1 months, 22.8 months, 18.3 months ,14.1 months in the UFS cohort. The NATCP staging demonstrated better accuracy compared with the AJCC staging system and was validated in the validation cohort. Conclusions: The NATCP staging provided better prognostic ability than the current AJCC staging system for resected PDAC regardless of the use of NAT and may facilitate clinical decision-making based on accurate prediction of OS of patients.