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Liquid biopsy vs. Signatera ctDNA cancer monitoring test



A deep dive into liquid biopsies vs. SignateraTM ctDNA cancer monitoring test

With newer cancer tests now available, it’s not surprising that cancer patients, survivors and their families are seeking information about every option to help them make the best decisions. In this blog post, we focus on Signatera and liquid biopsies, explaining what these tests involve, how they are performed, when they are used, and how they differ from each other.

For years, researchers have been working on improvements in cancer diagnostics, prognosis, and therapy, with a particular focus on developing less invasive, safer, and more effective cancer testing procedures. As a result of major scientific advancements over the past two decades, one method that has grown in popularity is the “liquid biopsy.” This procedure is used to identify cancer in a blood sample.
While liquid biopsies for cancer detection and management are not new, they have recently drawn considerable interest. Tumor cells were first identified in blood in the late 19th century, and the term “cell-free DNA” (cfDNA), which refers to fragmented DNA outside cells in the blood, was first reported in 1948. In the 1970s researchers found that patients with cancer tend to have an increased concentration of cfDNA in their blood.1 However, it was the recent development of powerful genomic technologies such as next-generation sequencing (NGS) that enabled sequencing of circulating tumor DNA (ctDNA, a type of cfDNA released specifically by cancer cells) and made the liquid biopsy approach to cancer diagnostics much more accurate and cost-efficient.2 Cancer is a molecular disease associated with genetic mutations, and this minimally invasive procedure can reveal the molecular signature of tumors to help inform a treatment plan and to determine how well treatment is working or if the cancer has returned.

What is a liquid biopsy?

The US National Cancer Institute (NCI) defines a liquid biopsy as “a test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood (CTCs) or for pieces of DNA from tumor cells that are in the blood (ctDNA).”3 For the purposes of this article, we are focusing on the second part of this definition, which involves the detection of ctDNA.
By Racheljunewong – Own work, CC BY-SA 4.0,
Most people are familiar with the concept of a traditional tissue biopsy. During this procedure, a doctor uses a needle or an endoscope or surgically removes some tissue that is then analyzed for the presence of cancer. Tissue extraction has several disadvantages, though: it is risky, painful, expensive, time consuming, and, in cases in which a tumor is difficult to access, not even possible. Additionally, because cancer evolves over time and patients need to be monitored before, during, and after treatment for remission or progression, tissue biopsies are too invasive to be used repeatedly.4
Unlike the tissue biopsy, a liquid biopsy simply involves collecting a sample of the patient’s blood for analysis, making this procedure minimally invasive, painless, and a lot faster and more affordable. It can easily be performed multiple times, allowing doctors to check the status of a tumor to see how well a treatment is working. Liquid biopsy also provides doctors with genetic information about the patient’s tumor. Today, NGS-based ctDNA sequencing can achieve much higher sensitivity (that is, correctly identify people who have cancer) than tissue biopsy.5
Liquid biopsy can be considered for all stages of the cancer-care continuum–from screening and diagnosis to therapy decisions, treatment response evaluation and post-treatment cancer surveillance–although today it’s mostly used in patients already known to have cancer. One of the biggest challenges of liquid biopsy is being specific enough (that is, correctly identifying people who do not have cancer) to avoid a false positive result in healthy people, as false positives may lead to anxiety and needless additional procedures.6

What is Signatera ctDNA cancer monitoring test?

The Signatera personalized, tumor-informed test is an innovative cancer-monitoring test that accurately detects ctDNA in your blood.

SIG three steps
Signatera can be used:
  • after surgery, to detect the presence of any residual disease
  • during treatment, to evaluate treatment response
  • after treatment, to monitor for early recurrence
The Signatera test is both highly sensitive and specific, meaning that if your test result is positive, there is a high likelihood that your cancer may recur without further treatment. If it is negative, the risk of recurrence is reduced. What makes Signatera unique is its ability to correctly identify the presence of molecular residual disease (MRD), or very small traces of cancer in the blood such as ctDNA).

The key differences between Signatera and liquid biopsies

Discover Signatera, a personalized, tumor-informed assay for patients previously diagnosed with cancer that accurately detects circulating tumor DNA in the blood.
  • Both blood and tissue vs. blood only: Unlike liquid biopsies, Signatera uses both your blood and tumor tissue to create a custom-built test that tracks your unique tumor DNA mutations. On the other hand, liquid biopsy may be useful for patients where tumor tissue is not available or ideal to extract.
  • Tumor-informed vs. tumor-naive: Signatera selects and tracks tumor mutations that are specific to your individual tumor and that would be present in all future cancer cells. This results in highly accurate cancer monitoring over time. Liquid biopsies use a tumor-naive approach based on detection of a predetermined panel of genetic alterations, making them less sensitive and specific.
  • Specific context vs. wider range of applications: Signatera is used in a specific context of MRD, cancer monitoring and treatment response, where it’s been proven to deliver exceptional accuracy. Liquid biopsies have been primarily used to identify actionable markers for therapy selection decisions or to predict treatment response.
If you have had cancer treatment, such as surgery to remove a tumor, you and your doctor will want to know as early as possible if any cancer cells are still present in your body. Knowing earlier if your cancer is likely to recur or has progressed after treatment can help you and your cancer care team make more informed decisions about additional treatment and future monitoring.


Additional Resources

Natera billing information for Signatera

Natera billing general information



1Su Y-H. Liquid biopsy: an old concept with a new twist. Genetic Engineering & Biotechnology News. April 18, 2019. Accessed September 23, 2020.

2Cheng F, Su L, Qian C. Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer. Oncotarget. 2016;7(30):48832-48841. doi: 10.18632/oncotarget.9453

3Liquid biopsy. National Cancer Institute. Accessed September 23, 2020.

4Marrugo-Ramírez J, Mir M, Samitier J. Blood-based cancer biomarkers in liquid biopsy: a promising non-invasive alternative to tissue biopsy. Int J Mol Sci. 2018;19(10):2877. doi: 10.3390/ijms19102877

5Chen M, Zhao H. Next-generation sequencing in liquid biopsy: cancer screening and early detection. Hum Genomics. 2019;13:34. doi: 10.1186/s40246-019-0220-8

6Mattox AK, Bettegowda C, Zhou S, Papadopoulos N, Kinzler KW, Vogelstein B. Applications of liquid biopsies for cancer. Sci Transl Med. 2019;11(507) doi: 10.1126/scitranslmed.aay1984