New cutoff of CA19-9 values for predicting pancreatic cancer using liquid biopsy.

Abstract

692 Background: Carbohydrate antigen 19-9 (CA19-9) is the biomarker most commonly used as a diagnostic aid for treatment efficacy and survival prediction for pancreatic ductal adenocarcinoma (PDAC). However, the cutoff value of CA19-9 is still being discussed. Instead, circulating tumor DNA (ctDNA) has been reported as a new biomarker for PDAC. Our previous study showed a correlation between CA19-9 levels and KRAS mutated ctDNA in the blood of PDAC patients. Based on this correlation, we validated an appropriate cutoff value for CA19-9 before surgery. Methods: We monitored continuously CA19-9 values and KRAS-mutated ctDNAs in unresectable PDAC patients (N=22) who underwent chemotherapy in 2015 to 2017. KRAS mutation in tumor tissues and mutated circulating tumor DNA (MctDNA) in plasma was analyzed for mutations by digital polymerase chain reaction (ddPCR) in 22 patients with pancreatic cancer. KRAS point mutation in plasma was analyzed, according to KRAS point mutation in tissue (ex. 12D, 12V). Receiver operating characteristics (ROC) curve analysis was plotted to determine new cutoff of CA19-9 value that emerged KRAS-mutated ctDNA in the longitudinal monitoring. Recurrence-free survival (RFS) and overall survival (OS) of 60 patients who underwent surgery for resectable PDAC in 2005 to 2013 were analyzed according to many survival variables including new cutoff of CA19-9 value and median CA19-9 before operation. Results: Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of RFS and OS in 60 patients who underwent surgery in 2005 to 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for RFS and OS in these patients (P = 0.010 and = P = 0.001, respectively), along with lymph node metastasis( P = 0.017 and P = 0.008), unlike the median CA19-9 level (P = 0.210 and P = 0.150). Conclusions: The results of this study demonstrate that preoperative 949.7 U/mL ≥ CA19-9 may be associate with poor prognosis in PDAC. In summary, our study demonstrated, for the first time, that the adjusted cutoff value of CA19-9 was an important biomarker for the prediction of recurrence and prognosis in patients with resected PDAC. Patients with high levels of CA19-9 before surgery had a higher risk of recurrence and poorer prognosis than those with low levels of CA19-9, therefore they may have benefitted more from drug treatment than surgical intervention. Nevertheless, appropriate clinical decision-making for patients with high CA19-9 levels should be confirmed in future clinical trials. Although our study results should be interpreted within the study limitations and further examinations are required to draw a definitive conclusion, we believe that it clarifies the selection of patients with PDAC.