Survival benefits of neoadjuvant chemo(radio)therapy versus surgery first in patients with resectable or borderline resectable pancreatic cancer: a systematic review and meta-analysis

Background Pancreatic adenocarcinoma is a highly lethal malignancy. Neoadjuvant chemo(radio)therapy [NAC(R)T] is recommended to use for borderline resectable pancreatic cancer (BRPC) and high-risk resectable pancreatic cancer (RPC), but no high-level evidence exists. Methods We searched PubMed, EMBASE, Web of Science, and Cochrane library to identify trials comparing survival data of NAC(R)T with SF for RPC or BRPC. Overall survival (OS) was synthesized in analysis of all the patients (intention-to-treat [ITT] analysis) and resected patients respectively. Results The meta-analysis included 17 trials with 2286 participants. For BRPC, NAC(R)T improved OS both in ITT analysis (HR, 0.49; 95% CI, 0.37–0.65; P < 0.001) and in analysis of resected patients (HR, 0.66; 95% CI, 0.51–0.85; P = 0.001) in comparison to SF, accompanied with comparable overall resection rate [odds ratio (OR), 0.69; 95% Cl, 0.41–1.16; P = 0.159]. Disease-free survival, R0 rate, and recurrence were also in favor of NAC(R)T. For RPC, OS in analysis of resected patients was higher with NAC(R)T (HR, 0.75; 95% CI, 0.63–0.89; P = 0.001), but OS in ITT analysis was similar (HR, 1.02; 95% CI, 0.85–1.22; P = 0.818). The overall resection rate (OR, 0.50; 95% Cl, 0.25–0.99; P = 0.048) was lower, but R0 rate was higher with NAC(R)T. No differences in disease-free survival and recurrence between NAC(R)T and SF. Survival benefits of NAC(R)T basically persisted across sensitivity and subgroup analyses. Conclusions This meta-analysis demonstrates that NAC(R)T can provide survival benefits in BRPC patients and a subgroup of RPC patients compared with SF. Future research should focus on investigating the potential biomarkers to screen the subgroup of RPC patients who can benefit from neoadjuvant therapy. Trial registration CRD42018103086.