Neoadjuvant chemoradiation therapy has positively altered the natural history of several cancers, especially esophageal and rectal cancer, and many investigators are looking at neoadjuvant therapy in the treatment of pancreatic cancer. I hope to give a brief overview of where we stand in 2006 in terms of neoadjuvant chemoradiation therapy for pancreatic adenocarcinoma.

Chemoradiation therapy prior to pancreatic cancer surgery has a number of potential advantages over postoperative therapy. First, pancreatic cancer can be considered a systemic illness in most cases and neoadjuvant therapy provides systemic treatment within days of diagnosis. Second, patients undergo systemic therapy prior to the huge physiologic insult of a pancreatic resection. They are therefore more likely to complete their therapy and less likely to have complications or delays associated with being in the relatively debilitated postoperative state. Following pancreatic cancer surgery, 25% of patients adjuvant therapy is not received, delayed or truncated due to complications, morbidity or patient refusal.Third, patients whose disease progresses during neoadjuvant therapy selfselect for aggressive tumor biology, never come to surgery and avoid the morbidity of a pancreatic resection during their short time of survival. Fourth, the sterilization of the operative field by neoadjuvant therapy might decrease the risk of disseminating microscopic tumor during resection and also result in fewer positive margins. Fifth, radiation therapy generally is more effective in wellvascularized preoperative tissue compared to relatively hypoxic postoperative tissues. Sixth, bowel in the irradiated field is resected at the time of surgery, decreasing long-term effects of irradiated bowel.

A disadvantage is that these patients usually require greater pretreatment preparation than patients who are expeditiously explored. Prior to neoadjuvant therapy a tissue diagnosis (usually fine-needle aspiration (FNA) via endoscopic ultrasound) is needed and biliary obstruction must be controlled (usually via an endoscopic biliary stent).Many patients also undergo diagnostic laparoscopy to rule out occult metastatic disease. There is also the possibility of making the surgery more difficult because of an irradiated field, however there is evidence that neoadjuvant therapy may actually decrease pancreatic leak complications following surgery. The biggest potential concern is the possibility that a resectable patient may progress to an unresectable patient during the course of therapy, thus missing the window of opportunity for curative resection. In the end, the clinical relevance of these possible advantages and disadvantages can only be determined through wellcontrolled, randomized, prospective trials which determine overall morbidity and survival.