Neoadjuvant treatment in resectable pancreatic cancer: Why is upfront surgery so hard to be beaten?

Neoadjuvant treatment is being extensively evaluated in pancreatic ductal adenocarcinoma (PDAC). This interest is appropriate given the dismal long-term prognosis for most patients who undergo upfront surgery. Despite prospective, retrospective and randomized trials supporting the role of neoadjuvant therapy in general for PDAC, the long-term benefit specifically for patients with resectable PDAC remains unclear. The phase III PREOPANC trial showed an improvement in overall survival in borderline resectable PDAC with neoadjuvant gemcitabine-based chemoradiation compared to upfront surgery alone, however, no such benefit was observed in the resectable cohort. Notably, three randomized trials (PANACHE01-PRODIGE 48, NORPACT-1, and PREOPANC-2) failed to show a clear improvement in overall survival with a neoadjuvant approach. The ongoing NeoFOL-R, PREOPANC-3, and the Alliance A021806 will help clarify the role of neoadjuvant therapy in resectable PDAC. In this minireview article we summarize the data surrounding neoadjuvant therapy in resectable pancreatic cancer and discuss future considerations of trials in this subgroup.