Circulating tumour DNA as a prognostic tool for surgically treated pancreatic ductal adenocarcinoma

Abstract

Introduction Pancreatic ductal adenocarcinoma (PDAC) has a high risk of early recurrence after surgery. We evaluated the utility of circulating tumour DNA (ctDNA) analysed at different time points as a prognostic tool. Secondary aims were prognostic value of ctDNA combined with plasma carbohydrate antigen (CA) 19-9 and prognostic value of peritoneal tumour DNA (ptDNA). Methods A total of 75 patients were included. Plasma samples were obtained preoperatively, 1 month, and 7–9 months after resection. Peritoneal lavage fluid (PLF) was collected preoperatively and 7–9 months after resection. Cell-free DNA (cfDNA) from plasma and ptDNA were analysed using mutation specific digital droplet PCR assays in a tumour-informed apprach. Kaplan-Meier survival curves, univariable, and multivariable Cox proportional hazard models were used to assess overall survival (OS) and recurrence-free survival (RFS). Results Preoperatively, detectable ctDNA was an independent risk factor for OS (HR = 1.88, p = 0.047). Detectable ctDNA 7–9 months after surgery was an independent risk factor for RFS (HR = 4.48, p = 0.017). Detectable ctDNA 1 month after surgery showed decreased RFS (HR = 1.98, p = 0.055). Preoperative, 1-month, and 7–9 months postoperative positivity for ctDNA and/or CA 19-9 showed a significantly worse median OS (p = 0.024, p = 0.008, and p = 0.0003). We did not find association of ptDNA with OS or RFS, but ptDNA detection 7–9 months after surgery was associated with peritoneal RFS (p = 0.003). Conclusion Our data indicate that detectable ctDNA in plasma taken before and 7–9 months after surgery holds independent prognostic value in PDAC. Combination of ctDNA with CA-19–9 may be a particularly strong prognosticator, which should be confirmed in future studies.