The Use of a New CellCollector to Isolate Circulating Tumor Cells from the Blood of Patients with Different Stages of Prostate Cancer and Clinical Outcomes - A Proof-of-Concept Study

Abstract

Background and MethodsCirculating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized. Forty-three PCa patients in different stages and 11 control subjects were studied. Some randomized samples were used to detect tumor-associated transcripts, such as prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA) and epidermal growth factor receptor (EGFR), in the isolated CTCs.ResultsThe mean CTC counts were 4.6 CTCs [range, 0–8] in patients with localized PCa, 16.8 CTCs [range, 10–25] in patients with locally advanced PCa, and 26.8 CTCs [range, 0–98] in patients with metastatic PCa. The median follow-up time was 24 months, and there was a significant difference in the cancer-specific survival rates. Patients with CTC counts under 5 CTCs lived significantly longer (p = 0.035) than patients with more than 5 CTCs. We also demonstrated that the captured CTCs could be molecularly characterized. We detected tumor-associated transcripts of EGFR and PSMA in patients with metastatic PCa in 42.8% and 14.3% of the analyzed samples, respectively.ConclusionOur results indicate that the sensitive isolation and molecular characterization of CTCs can be achieved ex vivo using the wire. Patients with more than 5 CTCs had a mortality risk that was 7.0 times greater that of those with fewer than 5 CTCs (hazard ratio 7.0 95%, CI 1.1–29.39). This proof of concept was required for the approval of the use of the CellCollector in a clinical study for the in vivo isolation of CTCs from the blood stream of PCa patients by the Federal Institute for Drugs and Medical devices (Germany, BfArM).

Improved detection of circulating tumor cells in non-metastatic high-risk prostate cancer patients

“…However, the number of isolated CTCs per sample was not significantly higher than obtained with the CellSearch system (CellSearch range 1–10, median 1.8; CellCollector range 1–12, median 2.4). Just recently, Theil and colleagues found a correlation between the number of CTCs captured by the CellCollector (cut off ≥5 CTCs) and overall survival18. However, this finding needs to be validated by additional and larger studies.…”

“…Thus, EpCAM-based enrichment alone cannot detect all CTC subpopulations21. Moreover, the usual restriction of analyzing large blood volumes from cancer patients22 could be circumvented by the in vivo CellCollector capture system1718, which resulted in higher incidences of CTC detection as compared to the CellSearch system. However, the number of isolated CTCs per sample was not significantly higher than obtained with the CellSearch system (CellSearch range 1–10, median 1.8; CellCollector range 1–12, median 2.4).…”

“…The aim of this study was to increase the sensitivity of CTC detection in patients with high-risk PCa through the combination of three complementary assays: (i) the epithelial cell adhesion molecule (EpCAM)-dependent CellSearch technology, which received FDA-approval for metastatic prostate cancer, (ii) the GILUPI CellCollector (CellCollector) that captures EpCAM-positive CTCs in vivo by an antibody-coated needle introduced in the arm vein171819, and (iii) the EpCAM-independent EPISPOT assay that enriches CTCs by negative depletion of leukocytes and detects viable prostate cancer cells based on their active secretion of PSA20. Peripheral blood was analyzed directly before and 3 months after radical prostatectomy (RP) to assess early dynamic changes in CTC counts, and the results were correlated to established risk factors.…”

Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy

“…It has been reported that nearly 30% of PCa cases overexpress EGFR and that deregulation of EGFR-mediated signaling pathways is associated with poor clinical outcomes [16,17]. Theil et al detected tumor-associated transcripts of EGFR in patients with metastatic PCa in 42.8% using CellCollector [18]. Shaffer et al detected EGFR expression in 18/20 (90%) of CTCs in patients with metastatic PCa using the CellSearch system [19].…”

Clinical Utility of Circulating Tumor Cells – A Clinician’s Current View

“…In the recent literature from 2010-2015, over 35 different CTC methods were identified [4]. More new devices have been recently described [5][6][7][8][9]. CTC detection modalities have been well documented [10][11][12] and will not be covered in this review.…”