Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide, according to the World Health Organization.

World Health Organization. Colorectal cancer. July 11, 2023.

The year 2020 witnessed over 1.9 million new cases and 930,000 deaths. These numbers are expected to rise by 63% and 73%, respectively, by 2040. 

Though it is rare in people under 50, affecting only 1%,

National Cancer Institute. Why is colorectal cancer rising rapidly among young adults? November 5, 2020.

cases in younger people have skyrocketed in recent decades, and are now twice as high as in the 1990s.

Dharwadkar P, Zaki TA, Murphy CC. Colorectal cancer in younger adults. Hematol Oncol Clin North Am. 2022;36(3):449–470.

Next-generation mt-sDNA

In 2014, the multi-target stool DNA (mt-sDNA) test, also called FIT-DNA and multitarget fecal DNA, was FDA-approved for screening in people with an average risk of CRC.

Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287–1297.

The test assesses DNA for mutation or methylation and hemoglobin levels in the stool, and showed higher sensitivity for detecting CRC than fecal immunochemical test (FIT) (92.3% vs 73.8%) but lower specificity (86.6% vs 94.9%), increasing the likelihood of false-positive results. 

Though the manufacturers recommend undergoing an mt-sDNA test every 1 to 3 years, it is typically done every 3 years. There is some evidence that it may help increase screening adherence and quality, and also clinical outcomes.

Eckmann JD, Ebner DW, Kisiel JB. Multi-target stool DNA testing for colorectal cancer screening: emerging learning on real-world performance. Curr Treat Options Gastroenterol. 2020;18(1):109–119.

Capsule endoscopy

Capsule endoscopy, also called capsule colonoscopy, is used to screen the colon for abnormalities, with research underway for potential benefits in CRC screening, specifically. 

This method requires the person to swallow a pill-shaped capsule equipped with a camera that takes pictures of the colon to be examined for any abnormalities. 

Its minimal invasiveness, avoidance of radiation exposure and associated risks, and the ability for a gastroenterologist to perform it, leading to potentially faster diagnosis, make it a promising method for increasing patient screening rates. However, its cost, bowel preparation requirement, and need for a follow-up colonoscopy are factors that may limit its adoption in clinical settings.

Hausmann J, Tal A, Gomer A, et al. Colon capsule endoscopy: indications, findings, and complications - Data from a prospective German colon capsule registry trial (DEKOR). Clin Endosc. 2021;54(1):92–99.

Virtual colonoscopy

Colonoscopy is the gold standard for CRC screening and diagnosis. The CDC recommends having this test every 10 years for people with average risk.

Centers for Disease Control and Prevention. Colorectal Cancer Screening Tests. February 23, 2023.

Colonoscopies are invasive—they involve thorough bowel preparation, sometimes require sedation, and are associated with complications like colon perforation and bleeding, all of which may discourage patients from participating in screening.

Chan SCH, Liang JQ. Advances in tests for colorectal cancer screening and diagnosis. Expert Rev Mol Diagn. 2022;22(4):449–460.

Virtual colonoscopy, also called computed tomographic (CT) colonography, is a painless and noninvasive screening method.

National Cancer Institute. Screening Tests to Detect Colorectal Cancer and Polyps. August 2, 2021.

As explained by the National Cancer Institute, it uses a CT scanner and a computer to display images of the colon that can be investigated for polyps and any abnormalities. It may also show pictures of areas surrounding the colon and thus unintentionally reveal other medical findings and diagnoses. The CDC recommends that virtual colonoscopy be done every 5 years. 

Its noninvasive nature and nonexistent risk of complications make it a more appealing screening method for patients; however, it still requires extensive colon cleansing. Unlike colonoscopy, virtual colonoscopy cannot remove polyps and other abnormal growths. A positive result requires a follow-up colonoscopy test. 

mSEPT9 test

The test showed a specificity of 80% for all stages of cancer, 68% sensitivity for detecting CRC overall, and only 64% sensitivity for detecting advanced disease, thus raising the potential for false negatives. The study that determined the performance of mSEPT9 in detecting CRC included only patients with known colon pathology rather than the general population. ​​

mSEPT9 test is also not associated with a decreased risk of CRC and mortality as it performs poorly in detecting precancerous lesions. This test isn’t approved for CMS reimbursement, and due to its insufficient sensitivity, it is not included in the latest USPSTF guidelines.

According to the National Cancer Institute, it is only recommended for people 50 years or older who don’t want to or can’t completely take standard CRC screening tests like FIT or colonoscopy. A positive test needs to be confirmed with a colonoscopy.

With the need for more convenient and less invasive screening methods, many blood-based tests are currently under research.

Collaboration among researchers, healthcare providers, government regulators, and industry players can help address these challenges.