The CellSearch™ System identifies and counts circulating tumor cells (CTCs) in a blood sample to predict progression-free survival and overall survival in patients with metastatic breast, colorectal or prostate cancer, and can do so earlier than the current standard of care. The contention is that the results of serial testing for CTCs with the CellSearch™ System provide additional information to the oncologist and does so earlier than other currently approved diagnostic modalities, thereby allowing the oncologist to make more-informed patient care decisions. The clinical use of CTCs has not been implemented for routine clinical practice for several reasons. Most notably, the lack of standardization and automation of the technology has required the use of laborious sample preparation procedures with corresponding high intra- and inter-laboratory differences in results. Furthermore, different reagents and methods are used for the staining and evaluation of immunocytochemically prepared slides in search of these rare events in blood and bone marrow, which can lead to differences concerning specificity and sensitivity. Finally, although peripheral blood is an ideal source for the detection of CTCs because of the noninvasive sampling procedure, the clinical significance of CTCs in peripheral blood is less clear than that for DTCs in bone marrow.
The technology has been validated in the sense that the CellSearch system enables the reliable detection of CTCs in blood and is suitable for the routine assessment of metastatic breast cancer patients in the clinical laboratory. Several studies show that serial estimation of CTC level up to 20 weeks correlates with progression-free and overall survival. This suggests that elevated CTC level at any time during therapy can reflect disease progression and mortality risk for MBC patients. Another subset analysis was done on 83 (of the 177) patients who were receiving first-line treatment for metastatic disease. CTC level was assessed in these patients at baseline and monthly thereafter for up to 6 months, for a median follow-up of 12.2 months. CTC levels before and after starting therapy were strong, independent prognostic factors for both progression-free and overall survival. It has not been proven, however, that it is a tool that improves clinical care.
Allard WJ, Matera J, Miller MC, et al: Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897-6904, 2004.
Cristofanilli M, Budd GT, Ellis MJ, et al: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781-791, 2004.
Hayes DF, Cristofanilli M, Budd GT, et al: Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 12:4218-4224, 2006.
Cristofanilli M, Hayes DF, Budd GT, et al: Circulating tumor cells: A novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420-1430, 2005.
Riethdorf, Sabine, Fritsche, Herbert, Muller, Volkmar, Rau, Thomas, Schindlbeck, Christian, Rack, Brigitte, Janni, Wolfgang, Coith, Cornelia, Beck, Katrin, Janicke, Fritz, Jackson, Summer, Gornet, Terrie, Cristofanilli, Massimo, Pantel, Klaus
Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer: A Validation Study of the CellSearch System
Clin Cancer Res 2007 13: 920-928