The combination of size-based separation and selection-free technology provides higher circulating tumour cells detection sensitivity than either method alone in patients with metastatic prostate cancer

Objective: To investigate the circulating tumour cells (CTCs) capture abilities of two technologies that are not dependent on cell-surface marker expression: a selection-free platform [AccuCyte^® -CyteFinder^® system (Rarecyte)] and a size-based platform [fluid-assisted separation technology (FAST)]. In addition, the combination of the two systems to more completely assess CTCs was investigated.

Patients and methods: In all, 28 patients with metastatic prostate cancer were included. Two 6 mL peripheral blood samples were taken from each patient at the same time-point. The samples were then subjected to the two different technology platforms in parallel. An additional group of samples was acquired by applying the waste chamber material from the FAST-group tests (flow-through that goes through the FAST filter membrane) to the Rarecyte system for the detection any CTCs that were not captured by FAST.

Results: The three groups had significantly different putative CTC-positive tests, with positive rates of 29% for Rarecyte, 57% for FAST, and 79% for the combination. We also assessed CTC phenotype: 56.6% of the CTCs were cytokeratin (CK)+/epithelial cell adhesion molecule (EpCAM)-, 3.1% were CK-/EpCAM+, and 40.3% were CK+/EPCAM+. The captured CTCs diameter ranged from 5.2 to 16.9 µm. The mean CTC size from the FAST waste chamber was significantly smaller. The diameters for each of the phenotypic groups were significantly different.

Conclusions: These data highlight disparities in the positive rates and enumerated CTC numbers detected by the two techniques. Notably, the combination of the two technologies resulted in the highest CTC-capture rates. Smaller CTCs were more likely to be missed by the FAST as they passed through the filter system. Sizes of CTCs varied with different cell surface marker phenotypes.