Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer

Simple Summary Pancreatic cancer is one of the deadliest cancers. It can only be cured by surgery, and most people with pancreatic cancer are diagnosed when the cancer is too far advanced to be able to be removed with an operation. Even when a patient can have surgery, in most instances, microscopic cancer cells will have already travelled away from the cancer and these will grow into new tumors, leading to the cancer's eventual return. Everyone who has surgery should also get chemotherapy in an effort to prevent the cancer from recurring. This review considers if giving at least some of this chemotherapy before surgery, as opposed to giving it all after surgery, is a better approach for some patients. This may be a good idea when other aspects of the cancer make it seem to be at a higher risk for having already spread, such as a high blood test tumor marker or a very large tumor. Additionally, there are different combinations of chemotherapy drugs that could be considered for use in treating these patients. The goal of this review is to summarize which patients might be good candidates for chemotherapy before surgery and how best to treat these patients. Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools.