Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer

Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda. In this Review, Besselink and colleagues discuss preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer, including disease staging and response evaluation. Key points Preoperative multi-agent chemotherapy (for example, FOLFIRINOX or gemcitabine plus nab-paclitaxel) is now routinely used in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC), both to obtain local and systemic control and to select suitable candidates for surgery. Considerable variation exists among national and international guidelines and clinical practices regarding preoperative therapy in patients with BRPC or LAPC, including the type and duration of chemotherapy and the role, type, and timing of radiotherapy; a uniform, evidence-based international guideline with support from all relevant societies is needed. Three randomized controlled trials reported improved outcomes with neoadjuvant chemotherapy or chemoradiotherapy compared with upfront surgery in patients with BRPC; more randomized trials assessing the effect of modern multi-agent chemotherapy and radiotherapy are needed and several