Adequacy of EUS-guided fine-needle aspiration and fine-needle biopsy for next-generation sequencing in pancreatic malignancies: A systematic review and meta-analysis.

Abstract

Background and objectives: A majority of pancreatic malignancies are unresectable at the time of presentation and require EUS-guided fine-needle aspiration or fine-needle biopsy (EUS-FNA/FNB) for diagnosis. With the advent of precision therapy, there is an increasing need to use EUS-FNA/FNB sample for genetic analysis. Next-generation sequencing (NGS) is a preferred technology to detect genetic mutations with high sensitivity in small specimens. We performed a meta-analysis to evaluate the adequacy of EUS-FNA/FNB for NGS in pancreatic malignancies.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from database inception to November 11, 2023. The primary outcome was the proportion of sufficient sample acquired by EUS-FNA/FNB in pancreatic malignancies for NGS. Secondary outcomes were the proportion of sufficient sample for NGS in pancreatic ductal adenocarcinoma (PDAC) and the detection rates of mutations in KRAS, TP53, CDKN2A, and SMAD4 and actionable mutations in PDAC. The pooled proportions were calculated using a random-effects model. Potential sources of heterogeneity were investigated with subgroup analyses and meta-regression.

Results: Twenty studies with 881 samples were included. The pooled adequacy of EUS-FNA/FNB sample for NGS was 89.9% (95% CI, 80.8%-96.7%) in pancreatic malignancies and 92.0% (95% CI, 81.3%-98.8%) in PDAC. Screening sample suitability before NGS testing was associated with lower adequacy in subgroup analysis (79.7% vs. 98.4%, P = 0.001). The pooled prevalences of mutations in KRAS, TP53, CDKN2A, and SMAD4 in PDAC were 87.4% (95% CI, 83.2%-91.2%), 62.6% (95% CI, 53.2%-71.7%), 20.6% (95% CI, 11.9%-30.8%), and 19.4% (95% CI, 11.2%-29.1%), respectively. The pooled prevalence of potentially actionable mutations in PDAC was 14.5% (95% CI, 8.2%-22.0%).

Conclusions: In the majority of cases, EUS-FNA/FNB can acquire adequate sample for NGS and identify tumor-specific mutations in patients with pancreatic malignancies. Strict pre-analysis screening criteria may negatively impact the sample adequacy and the success rate for NGS.