Does neoadjuvant treatment in resectable pancreatic cancer improve disease outcomes? Systematic review and metanalysis of randomized controlled trials.

704 Background: Neoadjuvant chemotherapy improves survival in borderline resectable pancreatic cancer (RPC). Whether these results are the same in upfront RPC is unknown. Methods: To evaluate the association of neoadjuvant treatment and outcomes in RPC a systematic review was performed including randomized trials of neoadjuvant treatment versus upfront surgery. Articles indexed in PubMed, Embase and Web of Science were evaluated. Data regarding treatment regimens, R0 rates, disease free survival (DFS) and overall survival (OS) were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Results: Of 3,229 abstracts, 6 randomized controlled trials were considered eligible with a combined sample size of 805 patients. Among the trials, the PACT-15, JSAP-05, and updated long-term results from PREOPANC and NEONAX trials were included. In the meta-analysis, we could see that neoadjuvant treatment in RPC does not improve DFS or OS; HR 0.72 [0.46-1.09] and HR 0.76 [0.52-1.11], respectively. Interestingly, R0 rates were improved about 20% with the neoadjuvant approach (HR 1.2 [1.04-1.37]). It is important to note that most studies evaluated gemcitabine-based regimens in the neoadjuvant setting. Conclusions: This metanalysis of six randomized controlled trials suggests that neoadjuvant chemotherapy with gemcitabine-based regimens does not improve PFS or OS in RPC compared to upfront surgery followed by adjuvant treatment. Neoadjuvant treatment improves R0 rates in about 20%. Randomized ongoing trials are eagerly waited with more active combined regimens including modified FOLFIRINOX.[Table: see text]