Preoperative CTC-Detection by CellSearch(®) Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer

SIMPLE SUMMARY: The survival after surgical removal of pancreatic cancer is remaining dismal with frequent cases of treatment failure by early cancer recurrence. There are currently no means to preoperatively identify those at risk for early recurrence. Circulating tumour cells (CTCs) have been shown to identify high-risk individuals in a variety of cancer types. We did explore the impact of CTC detection with the FDA-approved CellSearch(®) test on relapse and survival after removal of pancreatic cancer by surgery. CTCs were detected in about 7% of patients. The presence of CTCs in samples taken before the operation was associated with earlier cancer metastasis and shorter survival. The survival impact of CTCs was comparable to or exceeded the risk-factors that become available only after the operation like spread to lymph nodes or aggressive tissue growth patterns. We conclude that the detection of CTCs by this method warrants further exploration of its clinical application in presumed operable pancreatic cancer. ABSTRACT: In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5–10 years of follow-up. Preoperative samples were analysed by the CellSearch(®) system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.