• Predict progression-free survival and overall survival

• Monitor treatment response

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.

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

10 mL room-temperature whole blood (CellSave Preservative Tube); 7.5 mL minimum

Ship promptly; specimen must be tested within 96 hours. Provide collection date and time.

Allow at least 7 days after administration of doxorubicin before sample collection.

• 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

• CPT codes*:  88346 x2, 88361

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.

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.