Neoadjuvant chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: Meta-analysis and trial sequential analysis of randomized controlled trials

We aimed to compare resection and survival outcomes of neoadjuvant chemoradiotherapy (CRT) and immediate surgery in patients with resectable pancreatic cancer (RPC) or borderline resectable pancreatic cancer (BRPC). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards, a systematic review of randomized controlled trials (RCTs) was conducted. Random effects modeling was applied to calculate pooled outcome data. Likelihood of type 1 or 2 errors in the meta-analysis model was assessed by trial sequential analysis. A total of 400 patients from four RCTs were included. When RPC and BRPC were analyzed together, neoadjuvant CRT resulted in a higher R0 resection rate (risk ratio [RR]: 1.55, p = 0.004), longer overall survival (mean difference [MD]: 3.75 years, p = 0.009) but lower overall resection rate (RR: 0.83, p = 0.008) compared with immediate surgery. When RPC and BRPC were analyzed separately, neoadjuvant CRT improved R0 resection rate (RR: 3.72, p = 0.004) and overall survival (MD: 6.64, p = 0.004) of patients with BRPC. However, it did not improve R0 resection rate (RR: 1.18, p = 0.13) or overall survival (MD: 0.94, p = 0.57) of patients with RPC. Neoadjuvant CRT might be beneficial for patients with BRPC, but not for patients with RPC. Nevertheless, the best available evidence does not include contemporary chemotherapy regimens. Patients with RPC and those with BRPC should not be combined in the same cohort in future studies.