Prognostic utility of preoperative and postoperative circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Abstract

595 Background: Surgical resection offers the only chance of cure for localized pancreatic ductal adenocarcinoma (PDAC). Despite surgical resection, 80% of patients experience disease recurrence. There is growing evidence that support the prognostic role of perioperative KRAS-mutated circulating tumor DNA (ctDNA). We conducted a systematic review and meta-analysis to investigate the prognostic utility of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was performed in September 2021. We included studies that reported on the effects of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse free survival (RFS) in resected PDAC. The random-effects model was used to calculate pooled OS and RFS hazard ratios (HRs) and 95% confidence intervals (CIs). Publication bias was assessed by visual inspection of a funnel plot of the included studies. Results: We identified 6,986 studies, and 13 studies were eligible for analysis. A total of 954 patients were included for the final evaluation. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95% CI, 1.346-3.174; P < 0.001) and worse OS in 10 studies (HR, 2.170; 95% CI, 1.451-3.245; P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 7 studies (HR, 2.986; 95% CI, 1.897-4.699; P <.001), and worse OS in 5 studies (HR, 5.812; 95% CI, 1.757-19.228; P = 0.004) compared to negative ctDNA. There was visible symmetry in the funnel plot of the studies included, suggesting no publication bias. Conclusions: In resected PDAC, preoperative and postoperative KRAS-mutated ctDNA positivity may be useful markers of poor prognosis in terms of RFS and OS. Clinically, KRAS-mutated ctDNA testing may also have implications when considering the aggressiveness and duration of adjuvant therapy in PDAC, although prospective trials are needed to assess this utility.