Circulating tumor cell detection: a prospective comparison between CellSearch and Rarecyte platforms in patients with progressive metastatic breast cancer

Key findings

• The two platforms enumerated circulating tumor cells equivalently across 100 paired samples. At least one CTC was detected in 65% to 75% of samples, both platforms returned a median of 3 CTCs per 7.5 mL of blood, and the paired counts were strongly correlated (Spearman r = 0.823, p < 0.001).
• The density-based, enrichment-free platform met the validated prognostic cut-off as often as the reference method, and matched it even where low antigen expression might have separated the two. 48% of samples reached the five-or-more-CTC threshold versus 45% with the reference method, and in the triple-negative subgroup the paired counts stayed near-identical (R² = 0.994).
• Both platforms stratified overall survival at the five-cell threshold, the first such demonstration for the density-based platform. Among 86 patients, a count of 5 or more CTCs per 7.5 mL carried a hazard ratio of 4.21 (2.15–8.24, p < 0.001) by the density-based platform and 5.16 (2.58–10.34, p < 0.001) by the reference method.

The AccuCyte–CyteFinder workflow in the methods

“For the RareCyte test, a blood sample is collected in a 10 mL AccuCyte® BCT tube (RareCyte, Seattle, USA). 7.5 mL of this blood is transferred into an AccuCyte® Separation Tube. Subsequently, the tube is centrifuged and four layers are identified: plasma on top, then a broad gray layer of platelets, a thin layer of white blood cells (buffy coat), and finally a layer of compacted red blood cells. After centrifugation, the Separation Tube is clamped to create a barrier between the red blood cells and the rest of the sample. Plasma is then removed and replaced with a high density fluid. The buffy coat is retrieved after a second centrifugation. Then, transfer fluid is added to the buffy coat and after 10–60 min of incubation, the sample is applied to charged microscope slides with a spreading device. After drying, slides are processed using the Ventana DISCOVERY ULTRA automated platform. This platform applies fluorescently labeled antibodies against pan-CK and EpCAM, CD45, and a nuclear dye. The stained slides are scanned on a CyteFinder® digital microscope and candidate CTCs are identified using CyteMapper® image analysis software.”

— Dirix et al., Breast Cancer Research and Treatment (2022), Methods, “Measurement methods”

Why it matters for The AccuCyte–CyteFinder workflow users

If you are weighing an enrichment-free approach to circulating tumor cells, this study is a useful benchmark. Its central result is equivalence: counts from the AccuCyte–CyteFinder workflow tracked an established FDA-cleared reference method closely across 100 paired samples, and both separated patients at the same five-cell threshold. That distinction matters because the reference method enriches for EpCAM-positive cells before it looks, so a cell that carries little of that antigen can be lost before counting begins. The AccuCyte–CyteFinder workflow instead isolates nucleated cells by density and images them on slides, so the epithelial marker is read after the cells are captured rather than used to select them. For your own work the value is twofold: the workflow reproduced a validated prognostic cut-off head to head with an accepted standard, and it was the first time that threshold carried prognostic weight on this platform. When you need counts you can defend against an established method, showing that the two agree, and that yours also predicts outcome, is what earns a place in the workflow.