Role of neoadjuvant therapy in the management of pancreatic cancer: is the era of biomarker-directed therapy here?

Pancreatic cancer is the 4th leading cause of cancer-related death. Complete surgical resection (CR0) is considered the only curative treatment. Most patients present with unresectable or borderline resectable disease. Many small phase i/ii trials have tried to address the role of neoadjuvant treatment using chemotherapy with or without chemoradiation in the management of locally advanced disease. However, many of them looked at the rate of CR0 resection and the feasibility of such treatment. A trend for improved overall survival has been observed in the group of patients with borderline resectable disease who completed neoadjuvant treatment. A large proportion of patients progress while on treatment, sparing them from unnecessary surgery. We searched the PubMed database (using the key words "pancreatic cancer," or "pancreatic neoplasm," or "pancreatic adenocarcinoma," and "neoadjuvant treatment," or "neoadjuvant chemotherapy," or "neoadjuvant radiation therapy," or "neoadjuvant chemo-radiation," or "adjuvant therapy" [all fields] and "clinical trial" or "study") and abstracts presented at the American Society of Clinical Oncology meetings on gastrointestinal cancers. Here, we review the most recent papers that present results on neoadjuvant therapy in pancreatic cancer. All but one report used overall survival as an endpoint. Unfortunately, there are no valid biomarkers predicting tumour progression or recurrence, and response to treatment than can help to guide therapeutic choices. Our recommendation is to consider neoadjuvant treatment in cases of borderline resectable disease. In patients with primary resectable tumours, surgery followed by adjuvant treatment and enrollment on adjuvant treatment studies would be appropriate.