How to Choose the Best Circulating Tumor Cell (CTC) Test?

What Are CTCs?

Circulating Tumor Cells (CTCs) are cancer cells that detach from a primary tumor and enter the bloodstream, either as single cells or clusters. Detecting and analyzing these cells can provide critical insights into cancer progression and treatment planning.

Key Factors to Consider When Choosing a CTC Test

1. Test Sensitivity and Specificity
2.  Real-World Accuracy vs. Spiked Sampling
3.  Viability of Isolated Cells
4. Cost vs. Capability: Be Cautious About Low-Cost CTC Tests
5.  Accreditation and Compliance

1. Sensitivity and Specificity: Assessing the Accuracy of CTC Tests
The reliability of a CTC test hinges on its sensitivity (the ability to detect CTCs effectively) and specificity (the ability to accurately distinguish cancerous cells from non-cancerous ones). Different technologies vary significantly in their performance, and understanding these differences is critical for making an informed choice:

• Bead-Based Methods: Sensitivity of 50–60%, with limited marker selection that risks missing diverse CTC populations. This method is less reliable for clinical use.
• Flow Cytometry: Highly sensitive and specific, capable of detecting diverse CTC populations and preserving >99% cell viability for advanced analyses.
• PCR-Based Methods: Marker-specific but non-viable cells limit their use in further testing. Single-marker focus can miss diverse CTCs.
• Microscopy-Based Methods: Primarily for enumeration, with limited sensitivity and specificity. Non-viable cells restrict their application in advanced testing.
• Gradient Separation Techniques: Size-based isolation with inconsistent sensitivity and specificity. Cell viability is often questionable, reducing its utility for precise cancer management.

Each method has its strengths and weaknesses, but a critical factor to consider is the potential to detect diverse CTC populations accurately and preserve cell viability. Methods like flow cytometry stand out for their comprehensive capabilities, making them more suited for clinical and research purposes. When choosing a CTC test, understanding the technological limitations of each method ensures better-informed decisions and more accurate outcomes.

2. Real-World Accuracy vs. Spiked Sampling
Some laboratories claim sensitivity and specificity above 90%. However, these results are often based on spiked samples—artificially enriched with detectable cancer cells. This practice doesn’t reflect the complexity of real patient samples, potentially leading to overestimated performance metrics.
Be cautious of tests boasting exceptionally high accuracy without real-world validation.

3. Viability of Isolated Cells
To enable further analysis (e.g., molecular tests, drug sensitivity assays), the isolated CTCs must remain viable:

• Flow Cytometry with patented methodology : Ensures over 99% viability, ideal for drug sensitivity testing and personalized treatment.
• Other methods, such as PCR-based or microscopy techniques, fail to preserve viable cells, limiting their application.

4.  Cost vs. Capability: Be Cautious About Low-Cost CTC Tests

While low-cost CTC tests may seem appealing, they often come with significant limitations that can compromise the accuracy and reliability of the results. Many of these tests rely on technologies that are restricted to capturing CTCs based on a single marker, such as through positive selection. This means they may fail to detect the majority of CTCs, especially those that do not express the specific marker being targeted. As a result, these tests cannot represent the diverse population of CTCs in a patient’s bloodstream.
Moreover, the isolated cells from such tests are often non-viable, further limiting their utility. Without viable cells, advanced analyses such as drug sensitivity testing, molecular profiling, and gene expression studies cannot be performed. This lack of precision and comprehensiveness undermines the potential for accurate diagnosis and personalized treatment.
When evaluating CTC tests, it’s crucial to consider not just the cost but also the technology behind the test. Choosing a method that prioritizes accuracy, viability, and comprehensive detection ensures more reliable results and better outcomes for cancer management. Be cautious of technologies that cut corners, as they may ultimately hinder effective care.

5. Accreditation and Compliance
Ensure the laboratory conducting the test adheres to industry standards, such as:

• CLIA Certification: Establishes federal quality standards for lab testing.
  
• ISO Accreditation: Reflects global compliance with quality management and technical standards.

Comparison of CTC Testing Methods

What is the method for the RGCC CTC test? 

RGCC is using a flow cytometry technique, RGCC isolates CTCs to obtain a sample of cells that are 97-99% pure and 99% viable for testing purposes such as molecular analyses, immunophenotyping, gene expression tests, and sensitivities against various agents.

The sensitivity and specificity of the test are reported at 86.2% and 83.9%, respectively, based on real-time sampling rather than spiked samples.

Why Choose RGCC’s CTC Test?

• Sensitivity and Specificity: RGCC CTC tests has 86.2% sensitivity and  83.9% specificity based on real-time sampling rather than spiked samples.
• Reduction of False Negatives: High sensitivity in testing is critical to reduce false negatives, which can delay diagnosis and treatment. With the ability to detect EpCAM(+) cells in body fluids, flow cytometry can lead to fewer false negatives compared to other methods like cytology, enhancing the reliability of cancer screening.
• Accuracy in Diagnosis: Accurate detection of CTCs is essential for diagnosing malignancies, especially in patients with suspected metastatic disease. A more sensitive method can identify more cases of cancer, which can lead to timely and appropriate treatment.
• Viability: RGCC tests have more than 99% of viability of the isolated cells from the flow cytometry technique. With this high viability of RGCC tests, we can directly analyze over 50 chemotherapeutic drugs, 60+ targeted drugs, and 50+ natural substances on cancer cells to see which are effective for the patient’s body and their cancer type.
• Personalized Treatment: Analyzing CTCs provides insights into the genetic and molecular diversity of tumors, which can guide personalized therapy. The right testing method can help monitor CTC levels during treatment, assessing the response and risk of metastasis.
• Accreditation and Compliance: RGCC is accredited with IAS Accreditation Testing Laboratory & IAS Accreditation Medical Laboratory. IAS Accreditation ensures that laboratories and their results meet the highest levels of ethical, legal, and technical standards as defined by major international organizations.
  

  RGCC is also accredited with CLIA. CLIA (Clinical Laboratory Improvement Amendments) ensures that laboratories meet federal standards set by the Centers for Medicare & Medicaid Services (CMS), the Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) for quality and accuracy in laboratory testing.
  
  RGCC is also accredited with different international standards:
  ISO 22716: 2007 No: 20019220006394
  ISO 45001: 2018 No. 20152220006395
  

  RGCC is accredited by College of American Pathologists:
  

What is the further ability of the flow cytometry technique by RGCC? 

• The heterogeneity of CTCs refers to the variation in their characteristics, such as size, shape, and the presence of specific biomarkers, which can indicate different metastatic potential and responses to therapies. By using flow cytometry, researchers can detect and analyze these differences among CTCs, providing insights into the genetic and molecular diversity of tumors and potentially guiding personalized therapy for patients.
• Moreover, flow cytometry can identify specific cell populations within a heterogeneous sample, allowing for a more detailed understanding of the tumor biology and the dynamics of CTCs during cancer progression and treatment. Thus, flow cytometry serves as a valuable tool in understanding the complexities of tumor heterogeneity and its implications for cancer diagnosis and treatment.

RGCC: The Right Choice for CTC Testing

RGCC’s advanced CTC tests combine cutting-edge technology, rigorous compliance, and personalized insights, making them an invaluable tool for clinicians and patients seeking precise cancer care.

Reference:
https://www.sciencedirect.com/science/article/pii/S0009898123004539
https://pmc.ncbi.nlm.nih.gov/articles/PMC6675556/pdf/jciinsight-4-128180.pdf