Filipe C. Borges, Mafalda S. Pinto, Miguel F. Borges, Ana Alagoa João, Elsa Francisco, Marta Sousa, Marisa Aral, Vera Oliveira, José Filipe Cunha, Arianeb Mehrabi, Christoph Berchtold, Gil Gonçalves, Peter Bailey, Markus W. Büchler
SUMMARY OF BACKGROUND DATA: PDAC is the fifth leading cause of cancer-related death in Europe. Surgery is the only possible cure; however, recurrence is common. OBJECTIVE: This systematic review and meta-analysis aimed to assess the value of circulating tumor DNA (ctDNA) in pre- and post-surgery liquid biopsies as a prognostic biomarker for recurrence and survival in patients with PDAC. METHODS: We performed a systematic review and meta-analysis of studies identified in Medline (via PubMed) and Web of Science. The primary outcomes were disease-free survival (DFS) and overall survival (OS). RESULTS: 18 studies (965 patients) were included in the analysis. The presence of preoperative ctDNA was significantly associated with lower DFS (HR: 2.08; 95% CI: 1.63-2.65; P<0.00001) and OS (HR: 2.31; 95% CI: 1.66-3.22; P<0.00001). Postoperative ctDNA positivity was correlated with lower DFS (HR: 3.29; 95% CI: 2.10-5.15; P<0.00001) and OS (HR: 3.42; 95% CI: 2.06-5.67; P<0.00001). In a subgroup analysis, ctDNA presence was also significantly associated with worse OS in both upfront resection (HR: 2.04, 95% CI: 1.14-3.66; P=0.02) and neoadjuvant treatment (HR: 2.35; 95% CI: [1.56-3.54]; P<0.00001) subgroups. CONCLUSION: Both preoperative and postoperative ctDNA are significant negative prognostic markers in patients with PDAC undergoing surgery. In subgroup analysis, ctDNA maintained its prognostic value in both the upfront resection and neoadjuvant treatment groups. Monitoring ctDNA can help personalize treatment, specifically in the selection of patients for neoadjuvant, surgical, and adjuvant therapies.