Questions and Answers - Cancer Screening with Multi-Cancer Early Detection (MCED) Tests

What Are Cancer Screening Tests?

Cancer screening tests are used to check for cancer or signs of risk for cancer before a person has any symptoms. There are two kinds of benefits from cancer screening tests: earlier detection of cancer when it may be more treatable leading to improved survival and prevention of cancer in those found to be at risk.

What Kind of Tests are Used to Screen for Cancer?

Tests to detect cancer or cancer risk come in many forms:

  • Physical exams to check general signs of health. These exams can uncover signs of disease, such as lumps, abnormal moles or enlarged organs.
  • Imaging procedures, which take pictures of areas inside the body.
    • A mammogram is a screening test for breast cancer. This test is an x-ray picture of the breast. It has been shown to decrease the risk of dying from breast cancer.
    • Low-dose computed tomography (CT) is used to screen for lung cancer. It has been shown to decrease the risk of dying from lung cancer in heavy smokers. The procedure uses low-dose radiation to make a series of very detailed pictures of areas inside the body using a type of x-ray machine.
  • Direct observation tests, which involve visual examination of tissue for abnormal growths. A colonoscopy is a screening test for colorectal cancer. In this test, the rectum and colon are examined using a flexible lighted tube with a lens for viewing. A colonoscopy can find abnormal colon growths (polyps) in addition to colorectal cancer.
  • Laboratory tests, which analyze samples of tissue, blood, urine, or other substances in the body. For example, health care professionals take a sample of cervical cells to screen for cervical cancer with a Pap test.

Additionally, standard screening methods for colon and cervix cancers can detect a pre-cancer that can be removed (for example, polyps), and thus prevent the development of a cancer in addition to detecting cancer early.

Does a Positive Cancer Screening Test Mean I Have Cancer?

No. A screening test alone cannot diagnose cancer. A cancer screening test identifies something abnormal, and then more tests must be done to determine whether a person has a cancer and of what type. These are called diagnostic tests, and they may include a biopsy, in which cells or tissues are removed by a needle or during a surgical procedure so a pathologist can check them under a microscope for signs of cancer.

For example, a screening mammogram may find a change in breast tissue. This change may be a cancer or a pre-cancer or something else. More tests need to be done to find out what that tissue change means and whether it requires treatment or if it is a false-positive result.

Does a Negative Cancer Screening Test Mean I Do Not Have Cancer?

No. A screening test can miss the presence of cancer, leading to a false-negative test result. For example, mammograms may appear normal even though breast cancer is present. Overall, screening mammograms miss about 20% of breast cancers that are present at the time of screening.

What Are Multi-Cancer Early Detection (MCED) Tests?

Multi-cancer early detection (MCED) tests are tests that measure biological signals in body fluids that may be shed by cancer cells. These signals are also known as biomarkers or tumor markers. MCED tests are being developed to screen for cancers from more than one organ site at the same time. Like all screening tests, the MCED assay itself does not diagnose cancer. Depending upon which biological signals the MCED test measures, it may screen for several different types of cancers.

Current MCED tests measure different biological signals in blood plasma, such as:

  • Changes in DNA and/or RNA sequences,
  • Patterns of DNA methylation (a chemical change to DNA which changes how the gene product is expressed),
  • Patterns of DNA fragmentation (how the DNA is broken into smaller pieces),
  • Levels of protein biomarkers, and
  • Antibodies that a person may develop against components of growing cancer cells.

Research scientists continue to search for new technological approaches that may expand this list to measure even more biological signals (e.g., what your body’s immune cells are actively searching for).

What Kinds of Cancers Can Potentially be Found with Each MCED Test?

Most MCED tests measure different biological signals that may be shed by cancer cells. Depending on what is measured, the cancers that may be detected will vary. One MCED test may screen for colorectal cancer, bladder cancer, and prostate cancer, while another may screen for a different group of cancer types. To date, each MCED test under development looks for a different group of cancers.

We do not know if MCEDs will only find dangerous cancers or may also identify slow-growing cancers that might never affect a person’s health.

What MCED Tests are Available Now?

No MCED tests have yet been approved by the U.S. Food and Drug Administration (FDA). However, some companies are offering the tests to physicians and consumers as laboratory developed tests (LDTs), which are designed, manufactured, and used within a single laboratory; FDA has historically not enforced regulatory requirements for LDTs.

What Is Not Yet Known About MCED Tests?

There are many unanswered questions about the use of MCED tests to screen for multiple cancers. Some of the things that are not known include:

  • The entirety of benefits and harms of using MCED tests for cancer screening, including if the benefits outweigh the harms
  • Whether detection of cancers by MCED tests results in improved survival for screened individuals
  • Whether detection of cancers by MCED tests reduces deaths due to cancer
  • The appropriate diagnostic process following a positive MCED test

To date, no medical society has made recommendations to use MCED tests for cancer screening.

If MCED Tests are Looking for Many Kinds of Cancer, will the Test Say What Kind of Cancer a Person Has?

No. Some MCED tests indicate the likely organ site of the cancer (e.g., lung). Like other early detection tests, the MCED test only provides a signal for a possible cancer.

Additional testing, such as imaging, tissue biopsy, and surgery is required to diagnose if someone has cancer and if so, which kind of cancer.

How Many Follow-up Tests Might be Needed if an MCED Test is Positive for Cancer?

How much additional testing a person may need after an MCED test to determine if they have cancer, where that cancer is located, and what to do if those additional tests do not show a cancer, is unknown.

In addition, the follow-up tests after a positive MCED test come with potential harm to individuals in terms of the number of invasive procedures that might be needed to check all the possible cancer sites that could be involved, possible complications from those procedures, the time spent away from work, and anxiety and uncertainty about the testing process. (see below, “What are the potential harms of MCED tests?”)

What Are the Potential Benefits of MCED Tests for Cancer Screening?

The benefits and harms of MCED-based screening are unknown and require a randomized controlled trial to determine. Potential benefits of MCED screening might include:

  • Screening at organ sites currently without screening test. MCED tests may potentially detect cancers at organ sites where, currently, no screening is available, and perhaps save lives.
  • Earlier detection. MCED tests may potentially detect cancers that are hard to identify when those cancers are in an early stage. Finding cancer at earlier stage may improve the chance of cure or allow for less invasive treatments.
  • Screening for multiple cancers at the same time. MCED tests can potentially identify cancers from many different organ sites with only a single test, saving time and minimizing medical procedures.
  • Less invasive procedures. MCED tests rely on a blood draw, which may be more acceptable to patients than other forms of cancer screening tests.

Only randomized controlled trials that follow people over time and consider the complex set of factors involved in testing for multiple different kinds of cancers can determine if the potential benefits of MCED tests outweigh potential harms.

What Are the Potential Harms of MCED Tests?

The potential harms of MCEDs include:

  • False-negative results. An MCED test may report a negative result when the person has a cancer. In addition to delaying cancer treatment, false-negative results could provide a false sense of confidence that leads people to skip standard-of-care screening, such as regular mammograms.
  • False-positive results. An MCED test may report a positive result, but further diagnostic procedures do not find a cancer.
  • Overdiagnosis and overtreatment. Like other screening tests, MCED tests may not be able to tell the difference between cancers that grow slowly and may never become lethal from those that lead to illness or death.
  • Uncertainty and potential harms from procedures needed to diagnose the cancer. Some companies producing MCED tests provide a list of potential organ sites for the cancer to lead your health care provider in starting a diagnostic workup. However, a positive MCED test could potentially result in negative follow-up tests, leading to a prolonged process to find if any cancer is present that causes patient anxiety and financial expense. These follow-up procedures may carry their own risks and have the potential to cause physical harm.

Only randomized controlled trials that follow people over time and consider the complex set of factors involved in testing for multiple different kinds of cancers can determine how the potential benefits of MCED tests stack up against potential harms.

Do MCED Tests Address Health Disparities?

More research is needed to understand the impact of MCED tests on health disparities.

If MCED tests and tests needed to make a diagnosis are not widely available and affordable, inequities for minority, underserved, and vulnerable populations will increase. Plus, a screening test cannot address the availability and affordability of appropriate treatments.

MCED screening might also help narrow the disparities gap in cancer clinical care by increasing the participation rate with available cancer screening programs through improvement in access to screening of underserved and socioeconomically vulnerable populations.

What Research and Clinical Trials are Underway to Develop MCED Tests?

There are several studies in development to evaluate the effectiveness of MCED tests in detecting cancers in individuals without cancer symptoms. The National Health Service in the United Kingdom, for example, is enrolling people to a randomized controlled trial to see whether screening with MCEDs (in tandem with standard screening) reduces the occurrence of late-stage cancers, and possibly death, compared to standard screening alone. Research groups and companies are continuing to investigate additional approaches to develop new MCED tests.

What Research is NCI Doing on MCED Tests?

The potential of MCED tests is exciting, but clinical trials of these tests are needed to prove that their use can save lives. NCI is working on a broad template for how to conduct a clinical trial with this substantially new type of screening test. A key feature of such a trial is determining the clinical utility of MCED tests by measuring whether the tests result in fewer cancer deaths in the population of screened individuals compared to a control population. There are numerous MCED tests in development by a variety of groups, all of which will need clinical trials to understand their potential benefit.

In addition, NCI is funding the collection of blood samples from patients with cancer and healthy persons in order to establish a large bank of case-control samples, for use in evaluating some MCED tests in future studies.

What MCED Tests Are Currently Being Used for Cancer Care?

There are currently no MCED tests approved by the FDA. One MCED test available to people in the United States is the GRAIL Galleri™ test, a laboratory developed test that must be ordered through a healthcare provider. However, whether the use of MCED tests for cancer screening in asymptomatic people saves lives is unknown and needs to be assessed through randomized controlled clinical trials.

Do Health Insurance Plans Pay for MCED Tests?

Most people will have to pay out-of-pocket for the test, and possibly also the follow-on diagnostic procedures.

Why Are MCED Tests Sometimes Called “Liquid Biopsies”?

MCED tests are a subset of liquid biopsy tests since they analyze bodily fluids to detect signs all at once of any given type of cancer from any given organ source. Liquid biopsy tests, including MCED tests, do not diagnose cancer and diagnostic testing, such as a tissue biopsy, is still necessary for a definitive diagnosis of cancer.

The term “liquid biopsy” applies to a broader group of cancer tests, not just those intended for early detection, that analyze bodily fluids, like blood or urine, to detect a potential cancer-related abnormality. For example, there are liquid biopsies approved by the FDA as companion diagnostics. Many of these tests detect whether a cancer patient’s tumor has released DNA with specific genetic changes into their blood plasma, or other tumor markers. This information can guide decisions of whether certain cancer treatments might be effective for that individual’s cancer. Liquid biopsy tests could also be used to monitor patients after cancer treatment, to see whether the cancer relapses.

How Are MCED Tests Different from Genetic Tests?

While MCED tests analyze molecules released by tumor cells, genetic tests for cancer risk look for specific inherited patterns in a person’s genes, in healthy cells. Genetic variants can have harmful, beneficial, neutral (no effect), unknown, or uncertain effects on the risk of developing diseases. Harmful variants in some genes are known to be associated with an increased risk of developing cancer. These inherited variants are thought to contribute to about 5% to 10% of all cancers.

Genetic tests are usually requested by a person’s genetic counselor, doctor, or other healthcare provider who has reviewed the individual’s personal and family history. The genetic test options from which a health professional may select include those that look at a single gene and those that look for harmful variants in multiple genes at the same time. MCED testing is currently done by blood draws. Genetic testing is done on a small sample of bodily fluid or tissue—usually blood, but sometimes saliva, cells from inside the cheek, or skin cells. The sample is then sent to a laboratory that specializes in genetic testing. The laboratory returns the test results to the doctor or genetic counselor who requested the test.

Selected References

Etzioni R, Gulati R, Weiss NS. Multi-Cancer Early Detection: Learning from the Past to Meet the Future. Journal of the National Cancer Institute 2021; djab168.

Mattox AK, Bettegowda C, Zhou S, et al. Applications of Liquid Biopsies for Cancer. Science Translational Medicine 2019; 11(507):eaay1984.

Sorbara L, Srivastava S. Liquid Biopsy: A Holy Grail for Cancer Detection. Biomarkers in Medicine 2019: 13(12):991-994. 

Related Resources

Cancer Screening Overview (PDQ®)
Screening Tests
Tumor Markers