Analyzing high blood volumes for CTCs via DLA significantly improves detection and identifies pancreatic ductal adenocarcinoma patients with poor prognosis

Background Circulating tumor cells (CTCs) are associated with poor survival in patients with pancreatic ductal adenocarcinoma (PDAC). Because CTC-detection rates are low in M0-PDAC (~10%), only a small fraction of high-risk patients can be identified. Here we tested whether diagnostic leukapheresis (DLA), a clinically safe method that potentially allows to screen 2.5L peripheral blood (PB), can significantly increase CTC-detection rates in PDAC.

Methods Forty-six patients with PDAC who were scheduled for tumor resection were included. Both DLA and PB (7.5 mL) samples were obtained prior to surgery. DLA with was performed as previously described and CTC detection in PB and in DLA-samples (5% of whole DLA product) was performed using CellSearch^® (CS) and via ACCEPT software.

Results DLA led to a significant increase in CTC detection frequency (14.3% PB; 45% DLA) (p=0.003). Also, the CTC/mL increased 10-fold (0.08 PB; 0.82 DLA) (p=0.0008). We observed a significant negative prognostic impact for CTCs detected in DLA samples (p < 0.001), which remained even if higher CTC cut-offs were used (≥2 CTC: p = 0.01; CTC ≥ 3: p = 0.05). Interestingly, analysis of DLA revealed a clear prognostic separation of DLA^CTC-/M0 patients with a favorable long-term outcome. Multivariate analysis confirmed DLA CTC as independent prognostic factor of poor OS (HR 3.3; 95% CI 1.46-7.47; p = 0.004). The CTCs in matched PB samples were of no prognostic significance, most likely due to the expected low detection rate in a relatively small cohort.

Conclusions DLA can significantly increase CTC detection rates in PDAC, although we only investigated 5% of the DLA product here. Our data suggests that DLA CTCs identify patients with subclinical metastatic spread and poor prognosis. On the other hand, patients with locally advanced PDAC and negative CTC status in DLA samples displayed a relatively good prognosis. Hence, patients with primary PDAC and negative CTC-status might be good candidates for surgical treatments with curative intent, while patients with positive CTC-status may require more intensified multimodal therapy. DLA CTCs could thus provide a valuable tool for better patient selection.

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Artikel online veröffentlicht:
07. September 2021