Impact of Tumor Response After Neoadjuvant Treatment on Overall Survival Among Patients With Pancreatic Ductal Adenocarcinoma: National Cancer Database Analysis.

Background Complete pathologic response following neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is rare; alternative markers associated with survival are needed. The aim of this study was to evaluate the impact of tumor response to NAT on overall survival (OS) in PDAC patients who received NAT and curative-intent surgery. Methods A retrospective study utilizing the 2006-2018 National Cancer Database identified 6,960 adult patients with PDAC who received NAT. As a comparator group, 15,799 patients who underwent upfront surgical resection were separately analyzed. Primary outcome among patients who received NAT was OS according to changes in pathologic T and N staging compared to clinical T and N staging following NAT, defined as favorable response (downstaging) and non-favorable response (no change and upstaging).  Results After NAT, 35.1%, 43.4%, and 21.5% of patients had T downstaging, no change, and upstaging, respectively. Comparatively, 3.5%, 53.4%, and 43.1% of patients who underwent upfront surgical resection were over-staged, accurately staged, and under-staged, respectively, in reference to the T stage. Adjusting for patient, hospital, treatment, tumor, and margin status covarities, a favorable response to NAT, or T downstaging, was significantly associated with higher OS (HR 0.80, 95% CI 0.75-0.86; median OS 34.4 months, 95% CI 32.6-36.5) compared with a non-favorable response to NAT as the reference group (median OS 27.9 months, 95% CI 26.9-28.8). Similarly, a favorable response to NAT in the N stage was associated with a higher OS (HR 0.87, 95% CI 0.79-0.95; median OS 33.7 months, 95% CI 31.4-36.5) compared with a non-favorable response (median OS 29.3 months, 95% CI 28.6-30.3). Conclusion A favorable response to NAT is associated with higher OS among PDAC patients who underwent curative intent surgery.