Recurrence Following Neoadjuvant Therapy and Resection for Pancreatic Ductal Adenocarcinoma: A Comprehensive Meta-Analysis and Meta-Regression

Abstract

Background: This review aims to provide a comprehensive analysis of recurrence patterns in patients undergoing neoadjuvant therapy (NAT) in comparison to those undergoing up-front surgery (US) for PDAC. Methods: The EMBASE, SCOPUS, PubMed and Cochrane library databases were systematically searched to identify eligible comparative studies. The primary outcome was time to first recurrence and location of recurrence. Results: Twenty-five articles were identified including 4822 patients undergoing resection. The weighted mean follow-up interval for recurrence outcomes was 40.8months (CI 33.4-48.1). The weighted mean overall recurrence rate was 63.4% (CI 51.8-73.%) for NAT, significantly lower than the 74% (CI 68.7-80%) weighted overall recurrence rate of the US cohort (OR 0.67 (CI 0.52-0.87), P=0.006). NAT was also associated with a significantly longer weighted mean time to first recurrence (NAT 18.8months US 15.7months, P=0.015). The weighted locoregional recurrence (NAT 12%, US 27%, P=0.004) and liver recurrence (NAT 19.4%, US 30.1% P=0.023) rates were markedly improved among NAT patients. Weighted lung and peritoneal recurrence rates did not differ (P=0.705 and P=0.549 respectively). NAT was further associated with a greater two- (NAT 39%, US 22% OR 1.84 (CI 1.22-2.78), P=0.007) and five-year (NAT 24%, US 13% OR 1.95 (CI 1.03-3.69), P=0.043) recurrence free survival. Borderline resectability, presence of perineural invasion and a lower N0 nodal status were positive predictors of overall recurrence in the NAT cohort. Conclusions: NAT is associated with improved overall recurrence rates and longer time to first recurrence, an observation likely attributed to the improved rates of locoregional and liver recurrence.