Abstract
Pancreatic cancer has a dismal prognosis. Resection is the best option for cure, supported by multimodal therapy to treat the systemic disease. While adjuvant therapy has become standard in those who are fit and who can tolerate the given regimen, the concept of perioperative (neoadjuvant) therapy is building momentum. The concepts of "borderline" and "locally advanced" have changed the previous dichotomized "resectable/non-resectable" into subcategories for which new algorithms have emerged, with neoadjuvant therapy discussed both for upfront resectable pancreatic cancer, for those deemed borderline resectable, and as "induction or conversion" therapy for locally advanced disease. The purpose of this invited commentary is to discuss some of the changing paradigms in multimodal therapy for operable pancreatic cancer. The PREOPANC trial presented randomized data on the role of neoadjuvant therapy for resectable and borderline cancers, but new questions have emerged. The role of combination therapy in the preoperative setting is discussed in the light of this trial. FOLFIRINOX has emerged as the most potent treatment regimen in the metastatic and adjuvant setting, but with no level I data to support neoadjuvant use yet. Several trials are ongoing to arrive at the best answer.