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Update: Blood tests called liquid biopsies for cancer screening, monitoring and treatment

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Cancer screening tests Clinical trials
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Earlier detection is not always better Resources



Use of liquid biopsies in cancer care

Cancer screening tests

There are only five established cancer screening tests for people at average risk for cancer: colonoscopy for colon cancer, for breast cancer, Pap smears for cervical cancers, ( serum antigen) for cancer and low-dose CT (computer tomography) for those at high risk for lung cancer due to being a current or former smoker. People at high risk for cancer due to an may also have other types of cancer screening tests (e.g., breast or endoscopic to detect pancreatic cancer).

Because cancer screening tests are few and current screening tests are specific to a given organ, developing a reliable, simple test that could detect multiple cancers has been a goal of cancer research for decades.


When cells in the body die, their contents are released into the blood. Cell-free (cfDNA) is that has left the nucleus of a cell and floats freely in the blood. While everyone has some amount of cfDNA in their blood from normal cells, the blood of people with cancer may have some abnormal cfDNA from cancer cells. This is often called circulating tumor or .

In someone with cancer, the amount of is very small—about 0.1 percent of their total cfDNA. However, can be analyzed with advanced technologies to look for specific changes (mutations) found in cancer cells. When found, these mutations in the from tumors may indicate the type of cancer and even suggest possible treatments.

Liquid biopsies

Liquid biopsies look for bits of in the blood that are specific to cancer. An ideal would accomplish all the following goals:

  • detect a new or recurrent cancer at an earlier or more treatable than current screening
  • have a low “” rate (the test results is positive for cancer in a person who does not have cancer)
  • reduce the need for surgical biopsies and other invasive screening procedures
  • reveal the type of cancer or where it started
  • provide information on how to treat the disease

No test currently performs all these actions.

Liquid biopsies for people who are diagnosed with cancer

The has approved two tests to help guide treatment decisions for patients who are already diagnosed with cancer and likely have a lot of cancer in their blood. Guardant360 CDx, made by Guardant Health, is approved as a companion diagnostic for lung cancer therapy. FoundationOne Liquid CDx, made by Foundation Medicine, is approved as a companion diagnostic for ovarian, breast, lung and cancer therapies.

Other tests have been granted breakthrough designations. These are Signatera from Natera and RaDaR from Inivata to detect cancer recurrence.  Another test from Blue Star Genomics is used to detect pancreatic cancer in patients with new-onset diabetes.

Liquid biopsies as a screening tool for those without cancer

Significant progress had been made in recent years on the development of liquid biopsies to screen for and diagnose cancer in people who are not known to have cancer. Currently, three tests are available in the US for people who have not previously been diagnosed with cancer. None of these tests have been approved or given breakthrough designations. The tests—CancerSEEK from Thrive, PanSeer from Siglera Genomics and Galleri from Grail—are being marketed as tests that can detect multiple types of cancer at early stages. However, research on these tests is still early. Importantly, these tests are not recommended in expert guidelines to detect cancer yet.

false positives and false negatives

One of the challenges with liquid biopsies is that they need to be shown to be very “sensitive,” meaning that they can find cancers more effectively than current screening methods. Tests that are not very sensitive will have many “false negatives.” This means that the test will fail to detect cancers in people.

Liquid biopsies must also be proven to be “specific.” Tests that are not very specific will have many “false positives.” This means that they will incorrectly report that people have cancer when they do not. People with a test may have to undergo additional, invasive procedures to determine whether they do or do not have cancer.

The best way to know if a is sensitive and specific enough to be clinically useful is through a large, research study that shows the test can increase survival compared to standard screening. The biotechnology company Grail is beginning a large, prospective study involving 140,000 participants in the United Kingdom. The study will look at whether Grail’s Galleri multi-cancer early detection test is beneficial when compared to standard cancer screening tests.

Earlier detection is not always better

Finding some cancers at an early has been shown to decrease the chance of dying from that cancer. In contrast, finding and treating some cancers early do not improve the chance of a cure or help a person to live longer. While tests may eventually be able to detect more cancers at an early , early detection will not always mean fewer deaths.

In some cases, early cancer detection may do more harm than good. Some tumors may never grow enough to need treatment—any amount of treatment results in overtreatment. An ideal early detection test would distinguish aggressive tumors from slow-growing tumors.

These concerns highlight the need for careful evaluation of liquid biopsies and the tradeoff when it comes to current cancer screening methods, especially if screening many more healthy people identifies more cancers but at the likely emotional and financial cost of more false-positive cases in people who are cancer-free.

Health insurance coverage of liquid biopsies

Health insurance companies are most likely to cover the costs for tests that have solid evidence of improving outcomes and those that have been incorporated into national expert guidelines. Tests that are not part of guidelines may be available, but their benefits are unproven and out-of-pocket costs may be high.

What does this mean for me?

tests are playing an increasingly important role in cancer treatment. They may play a more prominent role in cancer screening as the research evolves.

If you are a person who has been diagnosed with cancer, ask your doctor if you might benefit from a test. These tests are especially helpful for:

  • advanced, recurrent or difficult-to-treat cancers.
  • cancers that are hard to reach for a tissue biopsy.
  • cancers for which treatment outcomes may be improved when recurrence is detected early.

If you are at high risk for cancer, it’s important to follow national expert guidelines for cancer screening and prevention. Talk with your healthcare professional about additional screening or whether you qualify for an early detection research study.

Read our related blog: Headline Hype: One simple blood test to detect 50 cancers? Not yet.

Share your thoughts on this XRAY review by taking our brief survey.  

Posted 9/29/2021


Klein EA, Richards D, Cohn A, et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Annals of Oncology. 32(9):1167-1177. Published online June 24, 2021.

Nadauld LD, McDonnell CH III, Beer TM, et al. The PATHFINDER study: assessment of the implementation of an investigational multi-cancer early detection test into clinical practice. Cancers (Basel). 2021; June 13; 13(14):3501.

Chen X, Dong Z, Hubbell E, et al. Prognostic significance of blood-based multi-cancer detection in plasma cell-free . Clinical Cancer Research. 2021; 27(15):4221-4229. Published online June 4, 2021.



FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

This article is relevant for:

People considering a liquid biopsy to screen for cancer

This article is also relevant for:

healthy people with average cancer risk

people with breast cancer

people with ovarian cancer

people with prostate cancer

people with metastatic or advanced cancer

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Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • How do I know if I’m at high risk for cancer?
  • I’m at high risk for cancer; what types of screenings should I have and when?
  • I’ve completed treatment; should I have a to monitor for recurrence?
  • My cancer has recurred. Should I consider a to determine the best treatment?
  • What are the risks and benefits of having a ?

Open Clinical Trials
Open Clinical Trials

The following research studies are looking at  and cancer. 

Visit our Featured Research Page and Research Search and Enroll Tool to find additional studies enrolling people with, or at high risk for cancer. 

Updated: 12/26/2023

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