Neoadjuvant chemotherapy for primary resectable pancreatic cancer: a systematic review and meta-analysis

Background: Preoperative chemotherapy has shown benefits for locally advanced and borderline resectable pancreatic cancer. Neoadjuvant chemotherapy (NAC) has also been attempted in resectable pancreatic cancer (RPC); however, its role remains controversial. This study aimed to compare the clinical difference between NAC and upfront resection (UR) in RPC. Methods: Electronic databases including PubMed, Embase, Medline, Web of Science, ClinicalTrials. gov, and Cochrane Central Register of Controlled Trials were searched for relevant articles from inception to February 2019 that addressed the overall survival in patients with RPC treated with or without NAC to identify eligible studies. Eleven studies were included in the final meta-analysis. The quality assessment of the included studies was based on the Newcastle- Ottawa quality scale. Data of the unresectable rate, R0 resection rate, and positive lymph node rate were also extracted in each study for further analysis. Pooled hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CIs) were calculated to assess the strength of the association. Results: A total of eleven studies (eight cohort studies and three randomized controlled trials) involving 9773 patients were included. Ten of the eleven studies followed the "intention-to-treat" principle. NAC was found to be significantly associated with a higher R0 resection rate (P < 0.0001; OR = 2.62, 95% CI 1.70- 4.03) and increased negative lymph node rate (P < 0.00001; OR = 0.34, 95% CI 0.31- 0.37). However, compared with the UR group, NAC was related to a lower surgical resection rate (P = 0.0004; OR = 2.18, 95% CI 1.41-3.37). Overall, the NAC group exhibited no benefits in terms of overall survival compared with that in the UR group (P = 0.10; HR = 0.86, 95% CI 0.73-1.03). In the subgroup analysis, however, patients who received gemcitabine-based regimen as the NAC strategy had more favorable overall survival than that in the UR group (P = 0.04; HR = 0.75, 95% CI 0.57- 0.99). Conclusions: NAC may be associated with a lower resection rate; however, it is associated with an increased R0 resection rate and lymph node negative rate. Although overall survival was similar in patients with or without NAC, gemcitabine-based NAC might provide longer overall survival. Further largevolume, randomized controlled trials are needed to validate the improved prognosis of patients undergoing NAC.