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Implications of Neoadjuvant Therapy on Prognostic Factors in Pancreatic Ductal Adenocarcinoma: A Path Towards
Ammar A Javed1,2,3, Joseph R Habib1, Paul C M Andel1,4
1Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY.
Objective:
To investigate prognostic factors in the context of neoadjuvant therapy (NAT) and develop tools that can allow for accurate and personalized patient prognostication.
Background:
NAT might impact the prognostic ability of well-established clinicopathologic 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 with corresponding 95% CIs. Predictive models were developed and an interactive tool was created to predict survival independently in both groups.
Results:
Of 2760 patients with resected PDAC, 778 patients (28%) received NAT. Independent predictors for worse OS in chemo-naïve patients included age ≥65 years, markedly elevated carbohydrate antigen 19-9 (≥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 patients undergoing NAT included non-normalization of carbohydrate antigen 19-9 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).
Conclusions:
Prognostic factors for OS in patients with resected PDAC differ between patients undergoing chemo-naïve and NAT. Personalized prediction tools for OS in resected PDAC based on these specific factors are available online (www.pancpals.com/tools).
