Prognostic Factors for Borderline Resectable / Locally Advanced Pancreatic Ductal Adenocarcinoma Undergoing Resection

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Surgical resection remains the only treatment with curative potential. It has been previously suggested that a margin negative(R0) resection is associated with improved overall and progression-free survival for these patients. However, over 50% of the patient present with metastatic disease, and would therefore only be candidate for palliative treatment, while only less than 20% of the patients would be amendable to immediate surgery. The other 30% of the patients present with disease involving the adjacent vasculature that may jeopardize an ontologically complete tumor resection, categorized as borderline resectable (BR) or locally advanced (LA) PDAC. Neoadjuvant systemic chemotherapy and/or radiation therapy, or neoadjuvant treatment (NT), was initially proposed for patients with LA-PDAC to achieve R0 resection and has also become increasingly popular among patients with less advanced tumors. Current National Comprehensive Cancer Network (NCCN) guidelines recommend receipt of NT for all patients with high risk features, including those with a BR-PDAC. A growing body of evidence suggests that neoadjuvant treatment prior to resection can improve the prognosis of patients with BR/LA-PDAC by facilitating an R0 resection. On the other hand, the term “borderline resectability” was proposed to recognize that, in some of these patients, it is possible to achieve negative margins by upfront resection (UR). For this group, delaying surgery for NT deprives them of the only chance for curative resection. To date, most retrospective studies investigating the prognostic impact of NT vs. UR did not distinguish R0 and R1 resection. It remains unclear whether there are additional prognostic benefits of NT beyond facilitating R0 resection. In the neoadjuvant setting, specific clinicopathological variables influencing survival may change at different time points. Previous studies tend to merge all variables in to one single model. In this study, we investigated the prognostic factors of patients with BR-PDAC to clarify whether the benefit of NT were independent of its impact on R status. Furthermore, we set out to identify prognostic factors at diagnosis, restaging and postoperatively of patients with non-metastatic PDAC undergoing NT followed by resection.