Implications of Neoadjuvant Therapy on Prognostic Factors in Pancreatic Ductal Adenocarcinoma: A Path Towards Personalized Prognostication.

Objective: The aim of the study was to investigate prognostic factors in context of neoadjuvant therapy (NAT) and develop tools that can allow for accurate and personalized patient prognostication.

Summary Of Background Data: NAT might impact the prognostic ability of well-established clinicopathological factors in resected pancreatic ductal adenocarcinoma (PDAC).

Methods: Patients after resection for PDAC were identified from the Dutch Pancreatic Cancer Group Recurrence Database and institutional databases at NYU Langone Health and the Johns Hopkins Hospital (2014-2019). Patients were stratified into NAT and chemo-naïve groups. Overall survival (OS), calculated from the time of resection, was estimated using Kaplan-Meier and compared using log-rank tests. Prognostic factors associated with OS were assessed in both groups using univariable and multivariable Cox-regression analyses and presented using hazard ratios (HR) with corresponding 95% confidence intervals (95%CI). Predictive models were developed and an interactive tool was created to predict survival independently in both groups.

Results: Of 2,760 patients with resected PDAC, 778 patients (28%) received NAT. Independent predictors for worse OS in chemo-naïve patients included age ≥65 years, markedly elevated CA19-9 (≥500 U/mL) at diagnosis, higher AJCC-T stage (T3/4 vs T1/2), worsening AJCC N-stage (N2 vs. N1 vs. N0), poor tumor differentiation, perineural invasion, and microscopically positive resection margin (R1 vs. R0). Contrastingly, predictors for worse OS in NAT patients included non-normalization of CA19-9 after NAT (<37 U/mL), presence of nodal disease (N1/2 vs. N0 given no statistical difference between N1 and N2 disease), and grade of treatment response (moderate/poor vs. complete/near complete).

Conclusion: Prognostic factors for OS in patients with resected PDAC differ between chemo-naïve and NAT patients. Personalized prediction tools for OS in resected PDAC based on these specific factors are available online (www.pancpals.com/tools).