Medical Policy: 02.04.16
Original Effective Date: March 2008
Reviewed: October 2015
Revised: November 2014
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services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary
based on contract, and individual member benefits must be verified. Wellmark determines medical
necessity only if the benefit exists and no contract exclusions are applicable. This medical
policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
The prognosis of cancer patients is often determined by the occurrence of metastatic disease. Studies have suggested that the presence of circulating tumor cells (CTCs) in patients with metastatic carcinoma is associated with shortened survival. Quantifying circulating tumor cells might be a useful technique to provide an immediate assessment of response to chemotherapy rather than relying on changes in imaging studies and guiding cancer therapy.
CTCs are malignant cells that are found in the peripheral blood and originate from primary or metastatic tumors. CTCs could potentially provide prognostic information and could guide treatment decisions or aid in the monitoring of response to treatment. CTCs have been documented in multiple tumor types, such as breast, prostate, lung and colorectal carcinomas; the largest body of data comes from studies of women with metastatic breast cancer. CTCs have also been investigated as an additional prognostic factor in nonmetastatic breast cancer and could be used to determine the need for additional adjuvant chemotherapy.
Research over more than 10 years has focused the development of methodologies with improved sensitivity and specificity. Physical techniques such as size filtration, density gradient centrifugation, and microscopic morphology continue to be used. However, biological techniques such as immunomagnetic isolation, flow cytometry, immunofluorescent microscopy, reverse transcriptase-polymerase chain reaction (RT-PCR), polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH) have been added to provide required specificity.
The CellSearch™ system (Janssen Diagnostics, formerly Veridex) is an example of immunofluorescent technology. The technique involves identification of the circulating tumor cells in blood which are tagged using antibody-coated magnetic beads that recognize cell surface antigens. The cells are then labeled with fluorescent dyes, which can then be quantified by a semiautomated fluorescent-based microscopy system.
Numerous studies have reported the association of circulating tumor cells (CTCs) with prognosis and/or response to treatment in patients with various types of cancer. However, despite these correctional studies, to complete the causal chain, there must be evidence that patient management decisions based on CTC levels increase the duration or quality of life or decreases adverse events. Literature searches have not identified any published studies that prospectively evaluate patient treatment decisions and/or health outcomes in patients managed with and without the monitoring of CTCs.
While studies have shown that the level of circulating tumor cells (CTCs) is associated with the presence of metastatic disease and prognosis, the prospective use of this information to impact care has not been demonstrated. Given that insufficient evidence is available to evaluate the impact on patient management or health outcomes and additional remaining questions (e.g. the optimal cutoff to use for various conditions) the assessment of circulating tumor cells is considered investigational.
Practice Guidelines and Position Statements
American Society of Clinical Oncology (ASCO): Recommendations for the use of tumor markers in breast cancer, published in 2007, indicate that the measurement of CTCs should not be used to make the diagnosis of breast cancer or to influence any treatment decisions in those with breast cancer. They should not be used in the prevention, screening, treatment, or surveillance of breast cancer.
In 2015 ASCO updated their guideline, Use of Biomarkers to Guide Decisions on Systemic Therapy for Women with Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline which states: “Recommendations for circulating tumor markers: In patients already receiving systemic therapy for metastatic breast cancer, decisions on changing to a new drug or regimen or discontinuing treatment should be based on clinical evaluation, judgment of disease progression or response, and the patient’s goals for care. There is no evidence at this time that changing therapy based solely on circulating biomarkers results improves health outcomes, quality of life or cost effectiveness.” (Type: evidence based. Evidence quality: intermediate. Strength of recommendation: moderate)
National Comprehensive Care Network (NCCN): Their 2015 Clinical Practice Guidelines do not include recommendations regarding detection of CTCs used in the management of patients with breast, colon or prostate cancer.
National Academy of Clinical Biochemistry (NACB): In 2009, NACB issued a guideline on the use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancer.
The CellSearch™ system (Janssen Diagnostics, formerly Veridex) has received U.S. Food and Drug Administration (FDA) marketing clearance through the 510(k) process for monitoring metastatic breast cancer (January 2004), for monitoring metastatic colorectal cancer (November 2007), and for monitoring metastatic prostate cancer (February 2008). The system uses automated instruments manufactured by Immunicon Corp. for sample preparation (Cell Tracks® AutoPrep) and analysis (CellSpotterAnalyzer®), together with supplies, reagents, and epithelial cell control kits manufactured by Veridex.
Detection and quantification of circulating tumor cells is considered investigational in the management of patients with cancer.
While levels of circulating tumor cells may be associated with the presence of metastatic disease and prognosis, the prospective use of this information to impact care has not been demonstrated. The clinical utility of quantifying CTCs remains unproven at this time. Published data is inadequate to determine how such measurements should guide treatment decisions and whether those treatment decisions could result in beneficial outcomes. Given the insufficient evidence to evaluate the impact on net health outcomes, the assessment of circulating tumor cells is investigational for the management of cancer.
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*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.