This study assessed the prognostic significance of CTCs and the feasibility of pulmonary vein sampling at the time of surgical resection NSCLC. Significantly more CellSearch-enriched CTCs were detected in pulmonary blood than in matched peripheral blood, and the presence of pulmonary vein CTCs was an independent risk factor for lung cancer recurrence and death. CTMs were also detected in samples of pulmonary vein blood, and patients with detectable CTMs or two or more peripheral vein CTCs represented a high-risk subgroup with an eightfold increased risk for disease recurrence and sevenfold increased risk for death.
An important aspect of the study was the timing of pulmonary vein sampling. Blood was taken before tumor manipulation, vessel ligation, or lung resection to avoid as much as possible artifactual elevation of CTC number.5 The association of pulmonary vein CTC count with disease recurrence and reduced OS suggests that this may be a biologically important cell population reflecting tumor biology rather than being a consequence of surgery alone. This approach was safe with no complications reported. The detection of CTMs has been reported to increase the risk for lung cancer recurrence after resection.3 We have previously described the prognostic significance in SCLC of CellSearch-detected CTMs8 and postulate that CTMs have an increased ability to survive in the circulation.9 In vivo models also support evidence that CTMs have increased malignant potential.10 and 11
Three patients suffered disease recurrence despite negative CTC detection by CellSearch. Coexpression of epithelial cell adhesion molecules and cytokeratins is a requirement for CTC capture and assignment using the CellSearch platform. Although this subpopulation of CTCs is biologically important as evidenced by the association between CellSearch CTC detection and prognosis in numerous studies,3, 4, 12, 13 and 14 it may not provide a comprehensive assessment of total CTC burden. Subpopulations of CTCs that lose their epithelial phenotype (e.g., epithelial-to-mesenchymal transition) may become undetectable by CellSearch. To more fully assess CTC heterogeneity, the use of marker-independent platforms is required; however, no other platform has been through the vigorous validation process required for routine use in the clinic.