A comprehensive review and meta-analysis of CTC isolation methods in breast cancer

The application of circulating tumor cells (CTCs) as diagnostic and prognostic markers in oncology is gaining increasing importance in clinical practice. Currently, various methods exist for detecting CTCs in patients' biological fluids. This systematic review aimed to compare the efficacy of different techniques for isolating and detecting CTCs from blood, against the FDA-cleared CellSearch® technology, in breast cancer patients. We performed a systematic literature search using two databases (PubMed and the Cochrane Library) with the following terms: ("Circulating tumor cells" OR CTC) AND "breast cancer", covering the period from 2004 to April 2023. The primary outcome measured was the sensitivity, specificity, and overall accuracy of various CTC enrichment methods in comparison with the CellSearch® System. Secondary outcomes included the prognostic value of CTCs in evaluating response to treatment based on survival rates. Generally, a high level of agreement between CellSearch and other methods was observed in isolating CTCs from patients' blood with both metastatic and early-stage disease. Studies asserting the superiority of new methods over CellSearch frequently used clinically unvalidated cut-off thresholds for their patient cohorts. Additionally, these studies sometimes included different nonoverlapping patient cohorts and lacked a standardized chemotherapy treatment protocol, which could affect the quantitative changes in CTC. It is evident that methods simultaneously composed of physical and immunomagnetic approaches for CTC isolation significantly surpass CellSearch, which relies solely on the expression of specific markers on the CTCs' surface. The count of CTCs has been established as a predictive marker in terms of clinically important parameters namely progression-free survival (PFS) and overall survival (OS). The CTC-count value was significantly correlated with PFS and OS rates.