How to select the most appropriate adjuvant treatment after neoadjuvant treatment and resection for locally advanced pancreatic cancer?

Adjuvant chemotherapy (ACT) significantly improves survival of patients undergoing upfront surgery for resectable pancreatic cancer. After introducing the concept of neoadjuvant therapy (NAT) with potent chemotherapy regimens, long term survival has been achieved even in patients with borderline and locally advanced pancreatic cancer (BR/LAPC) following radical resection. The observed pathologic tumor response is strongly predictive of survival and provides a unique opportunity to visualize to what extent the cancer has been sensitive to the administered chemotherapy regimen and may potentially give hint how to personalize further oncologic treatment. Current literature provides only limited and heterogeneous data as to whether and what type of ACT is beneficial after NAT and resection for BR/LAPC. Larger studies suggest that ACT may bring survival advantage and should be attempted particularly in node-positive disease and preferably with more potent regimen such as FOLFIRINOX, if tolerable. In case of complete pathologic response, particularly after FOLFIRINOX, it does not seem beneficial to deescalate the treatment during ACT, but whether continuation on the same regimen is worthwhile needs to be further examined. In case of gemcitabine-based treatment as NAT, continuation with more cycles seems to be of value unless tumor biology proves to be too aggressive, with high lymph node ratio. Whether switch to a different regimen should be sought, if tolerability allows it, needs to be further studied. Whether it is the exact treatment sequence (NAT, ACT or both) of the potent chemotherapy regimens like FOLFIRINOX and gemcitabine-nab-paclitaxel or the total dose of chemotherapy that has impact on survival in BR/LAPC, is unknown.