New challenges in perioperative management of pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the industrialized world. Despite progress in the understanding of the molecular and genetic basis of this disease, the 5-year survival rate has remained low and usually does not exceed 5%. Only 20%-25% of patients present with potentially resectable disease and surgery represents the only chance for a cure. After decades of gemcitabine hegemony and limited therapeutic options, more active chemotherapies are emerging in advanced PDAC, like 5-Fluorouracil, folinic acid, irinotecan and oxaliplatin and nab-paclitaxel plus gemcitabine, that have profoundly impacted therapeutic possibilities. PDAC is considered a systemic disease because of the high rate of relapse after curative surgery in patients with resectable disease at diagnosis. Neoadjuvant strategies in resectable, borderline resectable, or locally advanced pancreatic cancer may improve outcomes. Incorporation of tissue biomarker testing and imaging techniques into preoperative strategies should allow clinicians to identify patients who may ultimately achieve curative benefit from surgery. This review summarizes current knowledge of adjuvant and neoadjuvant treatment for PDAC and discusses the rationale for moving from adjuvant to preoperative and perioperative therapeutic strategies in the current era of more active chemotherapies and personalized medicine. We also discuss the integration of good specimen collection, tissue biomarkers, and imaging tools into newly designed preoperative and perioperative strategies.

Keywords: Biomarkers; Neoadjuvant chemotherapy; Pancreatic ductal adenocarcinoma; Personalized medicine; Preoperative strategies.

Figure 1

Proposed pre-operative strategies to integrate biomarkers into clinical trials. ¹Patients’ selection based on predictive and prognostic biomarker; ²Functional imaging assessment. CT: Computed tomography; CRT: Chemoradiotherapy.

Figure 2

Proposed “neoadjuvant short window protocol” integrating tissue biomarker and dynamic imaging to monitor early response. EUS-FNA: Endoscopic ultrasound fine needle aspiration; MRI: Magnetic resonance imaging.