Preoperative Therapy for Pancreatic Cancer: The Tide Is Turning

Abstract

Removal of the primary pancreatic tumor and regional lymph nodes has long been touted as the only treatment modality that offers patients with pancreatic cancer a chanceat cure.However,historyhas taught us that pancreatectomy—when performed de novo—rarely cures. Indeed, most patients who undergo pancreatectomy develop cancer recurrence and die within 5 years of their operation. And, although the postoperative administration of systemic chemotherapy improves survival after surgery, it does so only modestly—when it is administered at all. Recognizing these realities, Tsai et al have presented a sound rationale for the routine delivery of preoperative therapy to all patients with technically resectable pancreatic cancer in this issue of Journal of Oncology Practice. The evidence reviewed by Tsai et al notwithstanding, an operation followed by systemic chemotherapy is still the standard treatment of patients with cancers that are localized and resectable, and proponents of that approach argue that it must remain so until high-level, randomized data are generated to supplant it. Unfortunately, preexisting biases have prevented that. The only two trials that have randomly assigned patients with resectable pancreatic adenocarcinoma to either de novo pancreatectomy or preoperative therapy (chemoradiation) followed by surgery opened in Europe and closed prematurely because of an inability to accrue patients. The larger European phase III NEOPAC study that randomly assigns patients to surgery with postoperative gemcitabine or preoperative gemcitabine and oxaliplatin followed by surgery and postoperative gemcitabine is anticipated to be more successful. Regardless, the existing data such as those reviewed by Tsai et al, although derived largely from preclinical models and single-arm phase II trials, already provide support for the premise that at least some patients may benefit from a strategy that is initially nonsurgical. So why must we wait for the results of a study that uses one single—and already somewhat antiquated—preoperative regimen before we move forward? We make confident clinical decisions all the time in oncology on the basis of data that are not nearly as strong as those that already exist today.