Improved risk stratification by circulating tumor cell counts in pancreatic cancer

Purpose: Pancreatic cancer is one of the most devastating diseases with a 5-year survival rate of 3-5%. Here we investigated if circulating tumor cells (CTCs) may predict metastatic spread and survival in pancreatic cancer patients. Experimental Design: In a prospective study we enrolled 69 pancreatic cancer patients. In peripheral blood CTCs were identified by MACS enrichment (anti-cytokeratin/anti-EpCam) and subsequent automated analysis after combined anti-cytokeratin/anti-CD45/DAPI staining. CTC results were correlated to established clinicopathologic risk factors, detection of disseminated tumor cells (DTCs) in bone marrow and clinical outcome (follow up time: 48 months). Results: Median patient survival was 11 months (0-48 months). Thirty-eight patients were male and 31 female, and the majority received gemcitabine (58/69). CTCs were present in 23/69 patients (33.3%) ranging from 1-19 cells (17 with >1CTC). While clinicopathologic parameters and DTC status did not correlate with CTC incidence, progression-free survival (PFS) and overall survival (OS) were significantly reduced in CTC-positive patients in univariate (p=0.009, PFS; p=0.030, OS, both logrank) and multivariate analysis (HR: 4.543; CI: 1.549-13.329; p=0.006, PFS; HR: 2.093; CI: 1.081-4.050; p=0.028, OS, both Cox regression). Also within patients receiving chemotherapy, PFS was significantly reduced in CTC-positive patients in univariate (p=0.013) and multivariate (HR: 4.203; CI: 1.416-12.471; p=0.010) analysis. Conclusions:  CTCs affect the outcome of patients with pancreatic cancer independent from other risk factors, including patients receiving (adjuvant) cytotoxic therapy. CTC stratification may allow a better upfront identification of patients with a longer life span who might profit from new adjuvant therapies.

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