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CellSearch Circulating Tumor Cells

CellSearch Circulating Tumor Cells

Test Summary

CellSearch® Circulating Tumor CellsTitle

  

Clinical Use

  • Predict progression-free survival and overall survival

  • Monitor treatment response

Clinical Background

Circulating tumor cells (CTCs), which are extremely rare in individuals without malignancy, are present at a wide range of frequencies in patients with various metastatic carcinomas.1 The assessment of CTCs may assist physicians in monitoring and predicting cancer progression and in evaluating response to therapy in patients with metastatic cancer.2,3 In particular, clinical studies have focused on metastatic breast,4-6 colorectal,7 and prostate8 cancer.

In multi-center prospective clinical trials, the number of CTCs determined using the CellSearch method was a significant independent predictor of progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast,5,6 colorectal,7 or prostate8 cancer. Before the start of therapy, levels of CTCs were used to stratify patients into a favorable or unfavorable prognostic group. In addition, serial monitoring of CTC count was useful to detect changes in patient prognosis, and detection of elevated CTCs at any time during therapy was an accurate indicator of rapid disease progression and shorter survival.9,10

Although not intended to replace imaging, CellSearch results may supplement imaging in the assessment of disease progression in patients with metastatic breast11 or colorectal cancer,9 Furthermore, in patients with metastatic breast cancer, the number of CTCs may predict treatment response earlier than imaging (3–4 weeks vs 8–12 weeks after initiation of therapy).5,11 Similarly, in patients with metastatic prostate cancer, CTC counts were earlier predictors of treatment response than reduction in prostate-specific antigen (PSA) levels, which are commonly used to evaluate disease progression (2–5 weeks vs 6–8 weeks).9

Since published literature has yet to demonstrate that the use of CTC measurements improves quality of life or increases survival, the American Society of Clinical Oncology (ASCO) does not recommend use of CTC measurements for diagnostic or treatment decision-making.12 However, the assay is FDA-cleared for the clinical uses stipulated above.

Individuals Suitable for Testing

  • Patients with metastatic breast, colorectal, or prostate cancer, prior to a new course of therapy and at follow-up

Method

  • Immunomagnetic cell enrichment using antibodies targeting epithelial cell adhesion molecule (EpCAM) and nucleus labeling with fluorescent dye

  • Epithelial cells distinguished from leukocytes using fluorescent-labeled monoclonal antibodies specific for epithelial cells (cytokeratins 8, 18, and 19) and leukocytes (CD45)

  • Results reported as number of CTCs/7.5 mL whole blood

  • Analytical sensitivity: 1 CTC/7.5 mL whole blood

Interpretive Information

A CTC count below the cutpoint suggests a longer PFS and OS, whereas levels above or equal to the cutpoint suggest a shorter PFS and OS (Table). During or following therapy, a CTC count above the cutpoint suggests lack of treatment response.

Table. Prediction of Survival Based on CTC Count9
CTC Count
(CTCs/7.5mL blood)		 Median PFS,
Monthsa		 Median OS,
Monthsa
Metastatic Breast Cancer  
Single measurement    

Baseline (prior to therapy)

    

<5

 7.0 21.9

≥5

 2.7 10.9

Follow-up (3–5 weeks after start of therapy)

  

<5

 6.1 21.7

≥5

 1.3 6.2
Baseline and follow-up measurement (15–20 weeks after start of therapy)

 At all time points <5

 7.2 22.6

Baseline <5; at last draw ≥5

 5.9 10.6

At all time points ≥5

 1.8 4.1

Baseline ≥5; at last draw <5

 6.1 19.8

Metastatic Colorectal Cancer

  
Single measurement    

Baseline (prior to therapy)

    

<3

 7.9 18.5

≥3

 4.5 9.4

Follow-up (2–5 weeks after start of therapy)

  

<3

 6.8 16.4

≥3

 1.9 4.4
Baseline and follow-up measurement (13–20 weeks after start of therapy)

At all time points <3

 8.1 18.6

Baseline <3; at last draw ≥3

 4.3 7.1

At all time points ≥3

 2.2 3.9

Baseline ≥3; at last draw <3

 7.2 11.7

Metastatic Prostate Cancer

  
Single measurement    

Baseline (prior to therapy)

    

<5

 5.8 21.7

≥5

 4.2 11.5

Follow-up (2–5 weeks after start of therapy)

  

<5

 6.5 20.7

≥5

 2.1 9.5
Baseline and follow-up measurement (13–20 weeks after start of therapy)

At all time points <5

 6.5 >26

Baseline <5; at last draw ≥5

 4.2 9.3

At all time points ≥5

 2.5 6.8

Baseline ≥5; at last draw <5

 7.3 21.3

CTC, circulating tumor cell.
a Median progression-free survival (PFS) and overall survival (OS) are calculated from the time of blood draw.

Antibodies used in the CellSearch assay are targeted at cell markers (EpCAM and cytokeratins 8, 18, and 19) expressed by adenocarcinomas. CTCs that do not express these markers will not be detected by the CellSearch assay, whereas circulating epithelial tumor cells from malignancies other than metastatic breast, colorectal, or prostate cancer may be detected. CellSearch test results should be interpreted in conjunction with other laboratory, clinical, and imaging findings. CellSearch and imaging results are not equivalent in assessing the transition between non-progressive and progressive disease.

References

  1. Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897-6904.

  2. Beerepoot LV, Mehra N, Vermaat JSP, et al. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol. 2004;15:139-145.

  3. Cohen SJ, Alpaugh RK, Gross S, et al. Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2006;6:125-132.

  4. Gaforio J-J, Serrano M-J, Sanchez-Rovira P, et al. Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis. Int J Cancer. 2003;107:984-990.

  5. Cristofanilli M, Budd T, Ellis M, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781-791.

  6. Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol. 2006;33:S9-S14.

  7. Sastre J, Maestro ML, Puente J, et al. Circulating tumor cells in colorectal cancer: correlation with clinical and pathological variables. Ann Oncol. 2008;19:935-938.

  8. Okegawa T, Nutahara K, Higashihara. Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol. 2009;181:1091-1097.

  9. CellSearch® Circulating Tumor Cell Kit (Epithelial) [package insert]. Raritan, NJ: Veridex LLC. LBL 50058, Rev. 6, 2009-05. Available at: http://www.veridex.com/pdf/7800047_04.pdf. Accessed August 11, 2009.

  10. Hayes DF, Cristofanilli M, Budd GT, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006;12:4218-4224.

  11. Budd GT, Cristofanilli M, Ellis MJ, et al. Circulating tumor cells versus imaging�predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006;12:6403-6409.

  12. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287-5312.
     
Content reviewed 12/2011
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