Analysis of Circulating Tumor Cells in Patients with Non-Metastatic High-Risk Prostate Cancer before and after Radiotherapy Using Three Different Enumeration Assays

Abstract

The characterization of circulating tumor cells (CTCs) can lead to a promising strategy for monitoring residual or relapsing prostate cancer (PCa) after local therapy. The aim of this study was to compare three innovative technologies for CTC enumeration in 131 high-risk patients with PCa, before and after radiotherapy, combined with androgen deprivation. The CTC number was tested using the FDA-cleared CellSearch® system, the dual fluoro-EPISPOT assay that only detects functional CTCs, and the in vivo CellCollector® technology. The highest percentage of CTC-positive patients was detected with the CellCollector® (48%) and dual fluoro-EPISPOT (42%) assays, while the CellSearch® system presented the lowest rate (14%). Although the concordance among methods was only 23%, the cumulative positivity rate was 79%. A matched-pair analysis of the samples before, and after, treatment suggested a trend toward a decrease in CTC count after treatment with all methods. CTC tended to be positivity correlated with age for the fluoro-EPISPOT assay and with PSA level from the data of three assays. Combining different CTC assays improved CTC detection rates in patients with non-metastatic high-risk PCa before and after treatment. Our findings do not support the hypothesis that radiotherapy leads to cancer cell release in the circulation.

Long-Term Dynamics of Three Dimensional Telomere Profiles in Circulating Tumor Cells in High-Risk Prostate Cancer Patients Undergoing Androgen-Deprivation and Radiation Therapy

“…Even though CTC collection from blood is a less-invasive method and can be used as a real-time liquid biopsy during regular follow-up [7], there are many challenges for the use of CTCs as a prognostic and/or predictive biomarker. For example, the number of CTCs found in patient samples depends on the isolation method used, because of CTCs immunophenotype heterogeneity, CTCs derived from the same tumor can present different expression of epithelial markers, such as EpCAM [15]. This difference might limit CTC detection by EpCAM-dependent technologies, like CellSearch [15].…”

“…For example, the number of CTCs found in patient samples depends on the isolation method used, because of CTCs immunophenotype heterogeneity, CTCs derived from the same tumor can present different expression of epithelial markers, such as EpCAM [15]. This difference might limit CTC detection by EpCAM-dependent technologies, like CellSearch [15]. In addition, many apoptotic CTC cells are also isolated and analyzed which may not necessarily be representative of potential metastatic cells; and, finally, CTCs can be absent in some non-metastatic PCa patients [15,16].…”

“…This difference might limit CTC detection by EpCAM-dependent technologies, like CellSearch [15]. In addition, many apoptotic CTC cells are also isolated and analyzed which may not necessarily be representative of potential metastatic cells; and, finally, CTCs can be absent in some non-metastatic PCa patients [15,16]. For a better clinical use of CTCs in PCa as a prognostic and/or predictive biomarker, a combination of enrichment (isolation), detection (identification), and characterization strategies (such as molecular profile), are necessary to improve our ability to identify high-risk lethal prostate cancer in patients with clinically localized high-risk prostate cancers [17,18].…”

The CAPRA score versus sub-types of minimal residual disease to predict biochemical failure after external beam radiotherapy

“…Using the Epithelial Cell Adhesion Molecule-based CellSearch® system, the frequency of patients positive for CPCs has been reported to be between 5% and 42% in patients with localised cancer [37,38], Comparing three different methods of CPC detection, the CellSearchÒ system detect CPCs in 14% of high risk patients, the EPISPOT assay in 42%Ò of patients and in 48% of patients using the CellCollectorÒ [39]. The differences and pitfalls of the different methods to detect CPCs have been reviewed [40].…”

Research Progress for the Clinical Application of Circulating Tumor Cells in Prostate Cancer Diagnosis and Treatment

“…Referring to the above findings, for CTCs to be better used for the early diagnosis and risk assessment of prostate cancer, the key is to improve the sensitivity and specificity of CTC sorting. Multiple groups have established various new CTC sorting platforms, such as the Thermoresponsive NanoVelcro CTC purification system [ 55 ], a high-density microporous chip filter [ 56 ], in vivo cell collector technology [ 57 ], an immunomagnetic micro/nanoparticle system [ 58 ], and a high-throughput acoustic separation platform [ 59 ], to contribute to PCa diagnosis. However, the prognostic value of CTCs remains limited to preclinical research and is not currently able to be used clinically for patients.…”