Locally Advanced Pancreatic Ductal Adenocarcinoma: Challenges and Progress

Pancreatic ductal adenocarcinoma (PDAC) is one of the major causes of death in the Western world, and it is estimated to become the second leading cause of tumour-related mortality in the next 10 years. Among pancreatic cancers, ductal adenocarcinomas are by far the most common, characterised by a challenging diagnosis due to the lack of initial and pathognomonic clinical signs. In this scenario, non-metastatic locally advanced pancreatic cancer (LAPC) accounts for a large proportion of all new pancreatic ductal adenocarcinoma diagnoses. There is no consensus on a common definition of LAPC. Still, it usually includes tumours that are not resectable due to vascular involvement. As of today, treatment is limited, and the prognosis is very unfavourable. Curative-intent surgery remains the gold-standard even if often jeopardized by vascular involvement. Continuing progress in our understanding of LAPC genetics and immunology will permit the development of different treatments, targeted or combined, including radiation therapy, hadrontherapy, targeted immunotherapies or new chemotherapies. A multidisciplinary approach combining various fields of expertise is essential in aiming to limit disease progression as well as patient outcome. Using a narrative literature review approach, the manuscript explores the most up-to-date knowledge concerning locally advanced pancreatic ductal adenocarcinoma management.