Localized tumors are divided into resectable, BR, and LA disease based on the venous and arterial involvement. Assessment of resectability is based on preoperative imaging, usually triphasic contrast-enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) with 1- to 2-mm slices. PDAC is deemed resectable if negative resection margins can be achieved.

Although R0 resections are defined differently, an R0 resection with a 1-mm tumor-free margin has been shown to correlate with improved survival compared to a <1-mm tumor clearance. The primary objective of surgery is to achieve a margin-negative (R0) resection. The aim of this study is to present a review of the current literature of NAT in the setting of resectable and BR/LA PDAC. Patients with particularly aggressive tumors that progress under NAT would not undergo surgical resection with the associated perioperative morbidity and mortality.

Patient selection is done according to tumor biology. With NAT, the proportion of patients receiving chemotherapy could be increased, leading to improved locoregional and systemic control of the disease. ДЄlmost half of the patients undergoing curative resection for PDAC do not receive adjuvant chemotherapy due to postoperative morbidity or a poor general condition. NAT may increase the rate of margin-negative (R0) resection in borderline resectable (BR) PDAC and downstage selected locally advanced (LA) tumors. The use of NAT in the treatment of PDAC has several potential advantages. With regard to PDAC, there is increasing interest in and experience of NAT in the form of chemotherapy or combined radiochemotherapy. In cancers of the esophagus, rectum, and stomach, the introduction of neoadjuvant chemotherapy (NAT) significantly improved outcomes. For allocation to the most suitable form of treatment, assessment of resectability at the time of diagnosis is of paramount importance. Due to the aggressiveness of the disease and the late onset of symptoms, only about 15вЂ“20% of the patients have a localized tumor at the time of presentation and therefore a chance of cure. The sole potentially curative treatment is surgical resection followed by adjuvant chemotherapy. Although the treatment of pancreatic cancer has improved over recent years, the prognosis is still dismal, with a 5-year survival rate of only 10% in Switzerland. The importance of PDAC will grow, as the prevalence is expected to rise. In 2020, pancreatic ductal adenocarcinoma (PDAC) was the tenth most common cancer, accounting for 3% of all new cancer cases, and the fourth leading cause for cancer mortality, responsible for 8% of all cancer deaths. This review summarizes the current evidence for NAT in resectable, BR, and LA PDAC, with a focus on high-level evidence and randomized controlled trials. The concept of NAT has recently been tested in resectable PDAC, but to date NAT has been restricted to clinical trials, as the data are limited and no clear benefits have yet been shown in this patient group. While NAT is routinely applied in locally advanced (LA) PDAC, there is increasing evidence demonstrating benefits of NAT in borderline resectable (BR) PDAC. Neoadjuvant chemotherapy (NAT), originally introduced to downstage tumor size, is nowadays more frequently used for selection of patients with favorable tumor biology and to control potential micrometastases.

PDAC treatment necessitates a multidisciplinary approach, and adjuvant chemotherapy after upfront resection is an established means of preventing recurrence. At the time of diagnosis, only about 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have resectable disease.

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