Abstract
The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68–0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82–1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71–0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.
Highlights
The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US)
NAT may be associated with the potential loss of eligibility for curative resection; presurgical attrition occurs in approximately 30% of patients with resectable PC, suggesting the possibility of selection bias in studies showing the benefits of NAT4,5
This pooled meta-analysis showed that the risk for overall mortality in patients with resectable PC was lower in NAT than that in US (HR 0.80, 95% confidence interval (CI) 0.70–0.92, P < 0.01)
Summary
The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). Systemic therapy has been adopted to neoadjuvant therapy (NAT) in borderline resectable PC based on the findings of several randomized controlled trials (RCTs) demonstrating its survival benefit[3] Nowadays, it is well accepted in the National Comprehensive Cancer Network guideline. The real effectiveness of NAT in resectable PC remains unclear, with conflicting results on survival gain compared with upfront surgery (US)[6,7] This meta-analysis www.nature.com/scientificreports aimed to investigate whether the effectiveness of NAT is superior to that of US in patients with resectable PC. We conducted subgroup analyses according to treatment strategy (NAT completed with surgical resection versus US completed with adjuvant therapy) and analytic method (intention-to-treat analysis (ITT) and per-protocol analysis (PP))
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