Catching cancer early before it spreads throughout the body can save lives. That’s why doctors recommend regular screening for several common types of cancer, using a variety of methods.
Colonoscopies, for example, screened for colon cancer, while mammograms screened for breast cancer.
While important, performing all of these tests can be logistically difficult, costly, and sometimes uncomfortable for patients. But what if a single blood test could simultaneously screen for the most common types of cancer?
That’s the promise of multicancer early detection testing, or MCED. This year, President Joe Biden identified the development of MCED tests as a priority for Cancer Moonshot, a US$1.8 billion federal effort to reduce the cancer death rate and improve the quality of life for cancer survivors. cancer and people living with cancer.
As a laboratory physician and researcher developing molecular tests for cancer, I believe MCED testing has the potential to transform cancer screening in the near future, especially if it receives strong federal support to enable innovation fast.
How MCED Tests Work
All cells in the body, including tumor cells, release DNA into the blood when they die. MCED tests look for traces of tumor DNA in the bloodstream. This circulating “cell-free” DNA contains information about the type of tissue it came from and whether it is normal or cancerous.
Tests to look for tumor DNA circulating in the blood are not new. These liquid biopsies – a fancy way of saying blood tests – are already widely used for patients with advanced cancer.
Doctors use these blood tests to look for mutations in the tumor’s DNA that help guide treatment. Since patients with advanced cancer tend to have a large amount of tumor DNA circulating in the blood, it is relatively easy to detect the presence of these genetic changes.
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MCED tests are different from existing liquid biopsies because they try to find cancer at an early stage, when there are not many tumor cells yet. Early detection of these cancerous cells can be difficult because non-cancerous cells also release DNA into the bloodstream.
Since most of the DNA circulating in the blood comes from non-cancerous cells, detecting the presence of a few molecules of cancerous DNA is like finding a needle in a haystack.
To make matters even more difficult, blood cells naturally release abnormal DNA with aging, and these strands can be mistaken for circulating cancer DNA. This phenomenon, known as clonal hematopoiesis, confounded early attempts to develop MCED tests, with too many false positive results.
Fortunately, new tests are able to avoid interference from blood cells by focusing on a type of “molecular barcode” embedded in cancer DNA that identifies the tissue it originated from. These barcodes are the result of DNA methylation, naturally occurring changes on the surface of DNA that vary for each type of tissue in the body.
For example, lung tissue has a different DNA methylation pattern than breast tissue. Additionally, cancer cells exhibit abnormal DNA methylation patterns that correlate with the type of cancer. By cataloging different DNA methylation patterns, MCED tests can focus on sections of DNA that distinguish between cancerous and normal tissue and identify the site of cancer origin.
There are currently several MCED tests in development and clinical trials. No MCED test is currently approved by the FDA or recommended by medical societies.
In 2021, biotech company GRAIL launched the first commercially available MCED test in the United States. Its Galleri test claims to detect more than 50 different types of cancer. At least two other US-based companies, Exact Sciences and Freenome, and a Chinese company, Singlera Genomics, have tests in development.
Some of these tests use different methods of detecting cancer in addition to circulating tumor DNA, such as looking for cancer-associated proteins in the blood.
MCED tests are not yet generally covered by insurance. GRAIL’s Galleri test is currently priced at $949, and the company offers a payment plan for people who have to pay out of pocket. Lawmakers have introduced a bill in Congress to provide Medicare coverage for MCED tests that gain FDA approval.
It is unusual for Congress to consider legislation devoted to a single lab test, which highlights both the size of the medical market for MCED and concerns about disparities in access without coverage for these expensive tests.
How to use MCED tests?
It will take many years to determine how MCED testing should be implemented in the clinic.
Researchers and clinicians are just beginning to ask questions about who should be tested, at what age, and how medical and family histories should be taken into account. It is equally important to establish guidelines for how physicians will further assess positive MCED results.
There are also concerns that MCED testing may lead to overdiagnosis of low-risk, asymptomatic cancers that are better left undetected. It happened with prostate cancer screening.
Previously, guidelines recommended that all men between the ages of 55 and 69 undergo regular blood tests to determine their levels of PSA, a protein produced by cancerous and non-cancerous prostate tissue. But now the recommendation is more nuanced, with screening suggested on an individual basis that takes into account personal preferences.
Another concern is that further testing to confirm positive MCED results will be costly and a burden on the medical system, particularly if a full body scan is required. The outlay for an MRI, for example, can run into the thousands of dollars.
And patients who test positive for MCED but are unable to confirm the presence of cancer after extensive imaging and other follow-up tests may develop lifelong anxiety about a potentially missed diagnosis and continue to move on. expensive tests in an unsuccessful search for a tumour.
Despite these concerns, early clinical studies are promising. A 2020 study of more than 10,000 previously undiagnosed women found that 26 of 134 women with a positive MCED test were confirmed to have cancer.
A 2021 study sponsored by GRAIL found that half of more than 2,800 patients with a known cancer diagnosis had a positive MCED test and only 0.5% of those confirmed to have no cancer had a false positive test. The test gave the best results for patients with more advanced cancers, but detected around 17% of patients with very early-stage disease.
MCED tests could soon revolutionize the way clinicians approach cancer screening. The question is whether the health system is ready for them.
Colin PrichardProfessor of Laboratory Medicine and Pathology, School of Medicine, University of Washington
This article is republished from The Conversation under a Creative Commons license. Read the original article.