Could Blood Tests Make a Future Without Colonoscopy Possible?

Colorectal cancer is a common cancer that begins in the large bowel. As the 3rd most common cancer in both men and women worldwide, it poses an important health risk to both sexes. It can begin as benign growths called polyps .

It is difficult to give an exact percentage of colorectal polyps that become cancer over time, because this varies with polyp type, size, and other factors. Large adenomatous polyps (for example, larger than 1 cm) are generally more likely to become cancerous. Small adenomas carry a lower risk, and not every polyp becomes cancer.

Regular colonoscopy and polyp screening are important for early detection and treatment of polyps. If a polyp at risk of becoming cancerous is found, a doctor can remove it to prevent cancer from developing. However, colonoscopy requires preparation such as a special diet in the days before the procedure and bowel cleansing , and is performed under light anesthesia (sedation). This is why many people do not welcome colonoscopy. As a noninvasive alternative, liquid biopsy tests are being developed.

Expected to Enter Clinical Practice in the Near Future

The US plans to add blood-based biomarker tests for colorectal cancer (CRC) screening to its healthcare system. Guardant Health has completed a US premarket approval application for its blood-based Shield test for this purpose. If approved by the FDA (US Food and Drug Administration), the test could be covered by Medicare. Competing companies, including CellMax Life, Freedom, and Exact Sciences, are also developing blood tests for CRC. If successful, doctors and patients could have multiple FDA-approved test options within a few years.

David A. Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, said these tests would soon enter use. American Gastroenterological Association (AGA) President John M. Carethers said, "If blood tests are successful, colonoscopies could be reduced in the coming years." This idea is particularly exciting for multiple cancer detection (MCD) tests. The US National Cancer Institute (US-NCI) explained that the technology has the potential to detect asymptomatic cancers affecting several organs through a simple blood test called a liquid biopsy. Although some companies currently sell multiple cancer detection tests, few include CRC components. The most popular liquid biopsy test for early cancer detection is Galleri, which screens for more than 50 cancer types.

What Are Liquid Biopsy and the Galleri Test?

Liquid biopsy is a technology used to identify and monitor cancer cells through a blood test. GRAIL's Galleri test is the most common type of liquid biopsy and can detect more than 50 cancer types using methylation patterns in cell-free DNA (cfDNA) in a person's blood. Abnormal methylation patterns are associated with changes in gene expression that contribute to cancer growth.

The US National Cancer Institute (US-NCI) and FDA recognize the potential of multiple cancer detection tests and plan to support their development. While NCI prepares to launch a four-year pilot study involving 24,000 people, the FDA views blood tests for cancer as an important advance and aims to help companies bring these tests to market.

CellMax Life's CRC-specific screening blood test is currently considered the only test to have received an important breakthrough designation from the FDA. Freenome's chief medical officer says the FDA could begin reviewing parts of applications next year and potentially permit a blood test for asymptomatic, average-risk people to launch in 2025.

An Inconsistent Track Record

Although the idea of phasing out screening colonoscopies is appealing, past disappointments with colorectal cancer (CRC) blood tests should not be forgotten. In 2016, German company Epigenomics received FDA approval for a CRC blood test called Epi ProColon, but Medicare did not cover it. The Centers for Medicare & Medicaid Services (CMS) said EpiProColon could harm some patients and that more reliable alternatives were available. The US-CDC (US Centers for Disease Control and Prevention) has not yet secured reimbursement coverage for the 949-dollar Grail Galleri blood test either, and reimbursement agreements have been reached with only a few private insurers.

In 2021, the US government's Centers for Medicare & Medicaid Services (CMS) announced standards for covering blood-based screening tests for certain patients. Requirements include FDA marketing approval and specific test performance characteristics.

In 2023, CellLife Max announced that its blood test offered 92.1% sensitivity for detecting CRC and 54.5% sensitivity for detecting advanced adenomas, with 91% specificity. Similarly, in 2022, Guardant published results meeting the CMS standard, reporting 83% sensitivity and 90% specificity for CRC detection.

However, Asad Umar, chief of gastrointestinal cancers in NCI's Division of Cancer Prevention, emphasized that data on current multiple cancer screening tests are limited and doctors should be cautious in making recommendations. Umar noted that some doctors are concerned about false-positive and false-negative results. He said doctors should tell patients that there are insufficient data on how these tests should be used.

Barriers to Adoption

There are three key steps for companies seeking widespread acceptance of CRC blood tests:

1. FDA approval,
2. Medicare reimbursement coverage, and
3. An A or B recommendation grade from the USPSTF (US Preventive Services Task Force).

The USPSTF's 2021 colon cancer screening recommendations assigned an A grade for adults aged 50-75 and a B grade for those aged 45-49. Recommended screening methods include colonoscopy, stool tests, and fecal immunochemical tests. If CRC blood tests receive FDA approval, the USPSTF will guide doctors on how patients can use them.

Ransohoff notes that the USPSTF has a different role from the FDA and CMS. The FDA and CMS focus on tests' general safety and efficacy but do not make specific recommendations or perform benefit–harm analyses. The USPSTF, however, conducts its own detailed, evidence-based assessments of products' benefits and harms. According to Ransohoff, the USPSTF is the gold standard, examining preferences and outcomes quantitatively and issuing specific practice recommendations.

The Future of Colonoscopies and Blood Tests

In a podcast, Carethers said sensitive blood tests could take over much of colonoscopy screening, leaving colonoscopy for situations where it is most needed. He thinks that in 20-25 years, colonoscopy could become a purely therapeutic procedure, such as removing a polyp.

Ransohoff of UNC, however, said colonoscopy would remain in use even if alternative blood tests were effective, and many people with positive blood tests would need colonoscopy for diagnosis. Rather than completely replacing it, blood tests should complement colonoscopy and other screening tools. Doctors and patients should weigh the advantages and disadvantages of colonoscopy, which offers preventive treatment, against diagnostic blood tests.

• What Is Colonoscopy? Why and How Is It Performed?

Conclusion

Let us evaluate the potential of liquid biopsies in colorectal cancer screening using a SOAR Analysis .

SOAR is an acronym for Strengths, Opportunities, Aspirations, and Results. SOAR analysis can be considered a more positive, future-oriented version of SWOT analysis. It emphasizes businesses' strengths and opportunities and focuses on how they can achieve their goals.

Strengths:

1. Offers a less invasive and less uncomfortable alternative to colonoscopy.
2. Blood tests give patients and doctors more options and flexibility.
3. Liquid biopsy technology has the potential to detect multiple cancer types.

Opportunities:

1. The FDA and CMS want to support liquid biopsy and multiple cancer detection tests.
2. Manufacturers of liquid biopsy tests continue working to enter the market.
3. If blood tests are successful, the number of colonoscopies could be reduced in the coming years.

Weaknesses:

1. Colorectal cancer blood tests have been disappointing in the past.
2. Data on current multiple cancer screening tests are limited.
3. Doctors are concerned about false-positive and false-negative results.

Risks:

1. CRC blood tests need FDA approval, Medicare reimbursement coverage, and an A or B grade from the USPSTF.
2. Detailed assessments of products' benefits and harms are needed.
3. Rather than entirely replacing colonoscopy, blood tests need to complement it and other screening tools.