Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer

Abstract

Background Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. Experimental Design A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. Results CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, ρ < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cutoff of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76–0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17–4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01–1.88, p = 0.040). Conclusions CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

Incidence and risk factors for abdominal occult metastatic disease in patients with pancreatic adenocarcinoma

“…Smaller series have also correlated age, tumor size, unintentional weight loss, jaundice and diarrhea, CA 19‐9, and inflammatory markers as OMD predictors. Moreover, circulating tumor cells show promise as a preoperative biomarker for identifying patients at high risk of OMD, as two recent studies showed significantly elevated preoperative numbers of circulating tumor cells in patients with OMD when compared with non‐OMD patients …”

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

“…More recently, Court et al . () preoperatively enumerated CTC using the microfluidic NanoVelcro chip and reported that PDAC patients with occult metastatic disease had significantly more CTCs than PDAC patients with localized disease (median 7 CTCs vs . 1 CTC, P < 0.0001).…”

“…The expression of C-MET, CK20, and CEA mRNA detected by RT-PCR after MACS purification correlated with TNM stage (Zhou et al, 2011). More recently, Court et al (2018) preoperatively enumerated CTC using the microfluidic NanoVelcro chip and reported that PDAC patients with occult metastatic disease had significantly more CTCs than PDAC patients with localized disease (median 7 CTCs vs. 1 CTC, P < 0.0001).…”

Surgical and local therapeutic concepts of oligometastatic pancreatic cancer in the era of effective chemotherapy

“…Future diagnostic tools such as circulating tumor cells and serum micro-RNAs to predict resectability, prognosis, and response to chemotherapy are continuously evaluated in ongoing studies [71][72][73][74]. Another review on "Molecular biology in pancreatic ductal adenocarcinoma" by Søreide K et al in this journal gives further insight into this promising new field [75].…”