Systemic neoadjuvant chemotherapy in modern pancreatic cancer treatment: a systematic review and meta-analysis

BACKGROUND Pancreatic ductal adenocarcinoma remains a disease with a poor prognosis despite advances in surgery and systemic therapies. Neoadjuvant therapy strategies are a promising alternative to adjuvant chemotherapy. However, their role remains controversial. This meta-analysis aims to clarify the benefits of neoadjuvant therapy in resectable pancreatic ductal adenocarcinoma. METHODS Eligible studies were identified from MEDLINE, Embase, Web of Science and the Cochrane Library. Studies comparing neoadjuvant therapy with a surgery first approach (with or without adjuvant therapy) in resectable pancreatic ductal adenocarcinoma were included. The primary outcome assessed was overall survival. A random-effects meta-analysis was performed, together with pooling of unadjusted Kaplan-Meier curve data. RESULTS A total of 533 studies were identified that analysed the effect of neoadjuvant therapy in pancreatic ductal adenocarcinoma. Twenty-seven studies were included in the final data synthesis. Meta-analysis suggested beneficial effects of neoadjuvant therapy with prolonged survival compared with a surgery-first approach, (hazard ratio 0.72, 95% confidence interval 0.69-0.76). In addition, RO resection rates were significantly higher in patients receiving neoadjuvant therapy (relative risk 0.51, 95% confidence interval 0.47-0.55). Individual patient data analysis suggested that overall survival was better for patients receiving neoadjuvant therapy (P= 0.008). CONCLUSIONS Current evidence suggests that neoadjuvant chemotherapy has a beneficial effect on overall survival in resectable pancreatic ductal adenocarcinoma in comparison with upfront surgery and adjuvant therapy. Further trials are needed to address the need for practice change.