Detection and Phenotyping of Circulating Tumor Cells in High-Risk Localized Prostate Cancer

e15178 Background: Enumeration of circulating tumor cells (CTCs) using the CellSearch platform has prognostic value in patients with metastatic castration resistant prostate cancer. However, the prognostic value of CTC enumeration in high-risk, localized prostate cancer (HRLPC) remains undefined. Methods: Patients with HRLPC (defined by ≥1 of the following criteria: ≥ cT3a disease, Gleason score 8-10, or PSA > 20 ng/mL) who have chosen prostatectomy for their definitive management were prospectively identified. Patients were consented to receive 4 sequential 30 mL blood draws, each collected in 3 separate 10 mL EDTA tubes. The first 2 blood draws were conducted 2 weeks prior and immediately prior to surgery, while the second 2 blood draws were conducted 4-6 weeks and 3 months following surgery. Within 4 hrs of blood collection, the white blood cell (WBC) fraction was pooled and Ficoll purified. The WBC fraction was transferred to a CellSave tube, and CTCs were enumerated using the CellSearch system. Expression of CD133 and E-cadherin was characterized using the CellSearch system in patients with detectable CTCs. Results: Within 3 monthsof study initiation in Nov 2011, 19 of a planned 37 patients have been accrued. Median age in the cohort was 65 (range, 51-74), and the number of patients with Gleason score 8-10, ≥ cT3a disease, or PSA > 20 ng/mL was 16, 4, and 2, respectively. The majority of patients (17/19, or 89%) had only one high-risk feature. Mean baseline PSA for the cohort was 11.4 (range, 3.4-37). CTCs were detectable in 67% of patients prior to surgery, 27% of patients at 1 month following surgery and 67% of patients at 3 months following surgery. Amongst those patients with detectable CTCs, the median count was 3 (range, 1-7). Further, in these patients, CD133 and E-cadherin were detected in 44% and 46% of specimens assessed, respectively. Full details of these analyses will be provided at the time of the meeting. Conclusions: Using a modified methodology, CTC enumeration using the CellSearch platform is feasible in patients with HRLPC. Interestingly, markers of epithelial-mesenchymal transition and stem cell lineage are detectable in a proportion of patients with localized disease.

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Clinical Impact of Circulating Tumor Cells in Patients with Localized Prostate Cancer

Cells ◽

10.3390/cells8070676 ◽

2019 ◽

Vol 8 (7) ◽

pp. 676 ◽

Cited By ~ 11

Author(s):

Broncy ◽

Paterlini-Bréchot

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Early Stage ◽

Clinical Impact ◽

Localized Prostate Cancer ◽

Aggressive Cancer ◽

Highly Sensitive ◽

Prostate Cancers ◽

Suitable Marker

The main issue concerning localized prostate cancers is the lack of a suitable marker which could help patients’ stratification at diagnosis and distinguish those with a benign disease from patients with a more aggressive cancer. Circulating Tumor Cells (CTC) are spread in the blood by invasive tumors and could be the ideal marker in this setting. Therefore, we have compiled data from the literature in order to obtain clues about the clinical impact of CTC in patients with localized prostate cancer. Forty-three publications have been found reporting analyses of CTC in patients with non-metastatic prostate cancer. Of these, we have made a further selection of 11 studies targeting patients with clinical or pathological stages T1 and T2 and reporting the clinical impact of CTC. The results of this search show encouraging data toward the use of CTC in patients with early-stage cancer. However, they also highlight the lack of standardized methods providing a highly sensitive and specific approach for the detection of prostate-derived CTC.

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Circulating Tumor Cells as a Marker of Disseminated Disease in Patients with Newly Diagnosed High-Risk Prostate Cancer

Cancers ◽

10.3390/cancers12010160 ◽

2020 ◽

Vol 12 (1) ◽

pp. 160 ◽

Cited By ~ 4

Author(s):

Wojciech A. Cieślikowski ◽

Joanna Budna-Tukan ◽

Monika Świerczewska ◽

Agnieszka Ida ◽

Michał Hrab ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Disease ◽

Newly Diagnosed ◽

High Risk Prostate Cancer ◽

Intergroup Comparison ◽

Risk Prostate Cancer

The aim of this study was to investigate whether the enumeration of circulating tumor cells (CTCs) in blood can differentiate between true localized and metastatic prostate cancer. A cross-sectional study of 104 prostate cancer patients with newly diagnosed high-risk prostate cancer was conducted. In total, 19 patients presented metastatic disease and 85 were diagnosed with localized disease. Analyses included intergroup comparison of CTC counts, determined using the CellSearch® system, EPISPOT assay and GILUPI CellCollector®, and ROC analysis verifying the accuracy of CTC count as a maker of disseminated prostate cancer. The vast majority (94.7%) of patients with advanced-stage cancer tested positively for CTCs in at least one of the assays. However, significantly higher CTC counts were determined with the CellSearch® system compared to EPISPOT assay and GILUPI CellCollector®. Identification of ≥4 CTCs with the CellSearch® system was the most accurate predictor of metastatic disease (sensitivity 0.500; specificity 0.900; AUC (95% CI) 0.760 (0.613–0.908). Furthermore, we tried to create a model to enhance the specificity and sensitivity of metastatic prediction with CTC counts by incorporating patient’s clinical data, including PSA serum levels, Gleason score and clinical stage. The composite biomarker panel achieved the following performance: sensitivity, 0.611; specificity, 0.971; AUC (95% CI), 0.901 (0.810–0.993). Thus, although the sensitivity of CTC detection needs to be further increased, our findings suggest that high CTC counts might contribute to the identification of high-risk prostate cancer patients with occult metastases at the time of diagnosis.

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Characterization of circulating tumor cells in patients with localized high risk prostate cancer, post-prostatectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.110 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 110-110 ◽

Cited By ~ 1

Author(s):

Terence W. Friedlander ◽

Archana Anantharaman ◽

Christopher Welty ◽

Kreshnik Zejnullahu ◽

Jeffrey Hough ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Copy Number ◽

Large Scale ◽

Proportional Hazards ◽

Predictive Biomarkers ◽

Cox Proportional Hazards ◽

Definitive Therapy

110 Background: Approximately 15% of men with newly diagnosed prostate cancer (PCa) have high-risk features, many of these patients will recur despite definitive therapy. Better predictive biomarkers could allow for earlier detection of recurrence and change surveillance paradigms. The role of circulating tumor cells (CTCs) as biomarkers in this context is not well defined. Here, we evaluate the ability to detect CTCs from men with high risk, localized PCa after radical prostatectomy (RP) and correlate their presence with prospective clinical data. Methods: Blood samples from 31 patients with high risk, localized PCa were obtained 2-4 months post RP and sent to Epic Sciences on an IRB approved protocol. Nucleated cells were subjected to immunofluorescent (IF) staining for cytokeratin (CK), CD45, and AR N-terminus. CTCs were identified by fluorescent scanners using algorithmic analysis. Cytokeratin expressing (CK+) CTCs were enumerated and subsequently analyzed for AR expression and individually sequenced for copy number variation (CNV) and large scale transitions (LST, a surrogate of genomic instability). Patients were followed prospectively for biochemical recurrence, defined as detectable PSA. Progression free survival (PFS) was calculated using Kaplan-Meier and Cox proportional hazards. Results: CTCs were detected in 87.1% (27/31) samples with an average of 5.6 CTCs/ml (range: 0 – 22.87) detected per patient. AR expression was detected in 12.9% (4/31) of patients. Ninety-nine CTCs from 14 patients were amenable to LST and CNV analyses. 10.1% (10/99) CTCs from 7 patients exhibited higher ( > = 6) LSTs than control WBCs (95% WBCs had LST < 6). Copy number alterations were detected in CTCs in commonly mutated genes in PCa, including AR, MYC, and TP53 amplification and deletions in PTEN and RB1. Patients with higher CTC burdens exhibited a trend toward shorter PFS (hazard ratio: 1.65; 95% confidence interval: 0.7-3.86; p: 0.13). Conclusions: There was a high incidence of CTC detection after RP in this population using a novel platform. We observed a trend toward shorter PFS in those with higher CTC burden. Genomic alterations were detectable in CTCs and consistent with established CNAs in PCa.

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