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Diversity of assessing circulating tumor cells (CTCs) emphasizes need for standardization: a CTC Guide to design and report trials

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Abstract

Hematogenous spreading of tumor cells from primary tumors is a crucial step in the cascade to metastasis, the latter being the most limiting factor for patients’ survival prognosis. Therefore, circulating tumor cells (CTCs) have become a field of intensive research. However, the process of isolation and identification of CTCs lacks standardization. This article presents an overview of 71 CTC studies reported in PUBMED since 2000 and focusing on colorectal cancer. These studies are evaluated regarding standardization of CTC isolation and identification, marker proteins used, study population and blood sample quality management, clinical performance, and quality measures. Overall, standardization of CTC assessment seems insufficient. Thus, comparability of CTC studies is hampered and results should be interpreted carefully. We here propose a standardized CTC guideline (CTC Guide) to prospectively design and report studies/trials in a harmonized form. Despite the current interstudy heterogeneity, the data indicate that CTC detection is of clinical relevance and CTCs should be considered as a surrogate prognostic marker. Many studies indicate the high potential for CTCs as prognostic markers, e.g., in colorectal cancer treatment. However, standardized, large-scale multicenter validation studies are still needed to pave the way for clinical implementation of CTC detection that could ameliorate individualized medicine regimes.

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Funding statement

Grants from the Werner & Klara Kreitz Foundation and the Ad Infinitum Foundation are gratefully acknowledged. This review was supported by intramural funding of the University of Lübeck (#E20-2011) and performed on behalf of the “North German Tumorbank Colorectal Cancer” (DKH #108446; www.northgermantumorbank-crc.de) and the “Surgical Center for Translational Oncology—Lübeck” (SCTO-L; www.sctol.uni-luebeck.de).The funding institutions had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare that there is no conflict of interest.

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  1. Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    S. Bünger, M. Zimmermann & J. K. Habermann

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Bünger, S., Zimmermann, M. & Habermann, J.K. Diversity of assessing circulating tumor cells (CTCs) emphasizes need for standardization: a CTC Guide to design and report trials. Cancer Metastasis Rev 34, 527–545 (2015). https://doi.org/10.1007/s10555-015-9582-0

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