Colorectal cancer is the second leading cause of all cancer-related deaths. While the rate of colorectal cancer has decreased in Americans over the age of 50, it has increased in Americans younger than 50. 

Stanford Cancer Institute member Uri Ladabaum, MD, MS, professor of medicine (gastroenterology & hepatology), discussed current colorectal cancer screening recommendations and how screening tests may evolve to be more accurate and convenient.

Current colorectal cancer screening and prevention

Most colorectal cancers begin as precancerous polyps. Screening works by detecting polyps so they can be removed before turning into cancer and by catching early-stage colorectal cancer when it’s most curable. Ladabaum says that the decrease in colorectal cancer in people over the age of 50 is likely attributable, at least in part, to screening.

As a result of the increase in colorectal cancer in people younger than 50, the recommended age for the average-risk population to begin screening was lowered from 50 to 45. While the cause of this increase is currently unknown, scientists agree there couldn’t have been a fast enough genetic change to cause this increase. Other potential factors have been postulated, such as obesity, environmental changes in the food and water supply, or changes in the gut microbiome but without conclusive evidence on what is driving the increase. Ladabaum wonders if this increase is due to something unique in the younger cohort or if the older population would have also seen a rise but haven’t due to being screened regularly. 

Regardless of these contrasting trends, the absolute number of colorectal cancer cases in younger people is still much smaller than in older adults, who make up the majority of colorectal cancer diagnoses.

For primary prevention, healthy living, including a high-fiber diet rich in vegetables and only the occasional intake of red or charred meat, which are both associated with a higher risk of colorectal cancer, can help people decrease their risk of developing the disease. However, even people who are attentive to their health still have some risk and can develop polyps for reasons scientists don’t yet understand.

Colonoscopy vs. stool-based screening test

Colorectal cancer screening is most commonly performed through a colonoscopy or a stool-based screening test. Colonoscopy is the most common test in the U.S., but other countries have opted for stool-based tests based on cost benefits and other factors. A colonoscopy should be performed every 10 years and stool-based tests every one to three years, depending on the test. Both colonoscopy and stool-based tests are good options for the average-risk population. Patients should consult with their doctor and decide together which one is right for them. 

For higher-risk populations, guidelines recommend colonoscopy because it’s more sensitive to detecting precancerous polyps and cancer than stool-based tests. Higher-risk populations include people who have had polyps removed and are under surveillance and people with a family history of colorectal cancer. People with a family history should begin screening either at 40 years old or 10 years before the onset of colorectal cancer in their first-degree relative, which may mean people begin screening substantially earlier than age 45. If there’s a family history of developing cancer at a young age, doctors should suspect it may be due to one of the cancer genetic syndromes and refer those families to a cancer genetic evaluation.

Ladabaum says there’s some interest in using non-invasive stool tests for patients who are in surveillance after having had polyps removed but are otherwise low risk. For now, colonoscopy is the recommended mode of surveillance for all patients who have had polyps removed. He also indicates that there is a lot of interest in using artificial intelligence (AI) to improve colonoscopy, but the data on current AI applications are mixed.

“Can we make colonoscopy better so we miss fewer things? There are issues of how careful people are when they’re looking and examining the colon for polyps. My hope is that there will be more developments in artificial intelligence applications that help us do a high-quality exam, not miss polyps, and help characterize polyps when they’re found.”

Blood-based colorectal cancer screening tests

Ladabaum says that screening strategies other than colonoscopy shouldn’t aim to find every polyp but should instead target advanced precancerous lesions and early-stage cancers.

“We don’t need to find all the non-advanced polyps if we can later find the ones that are progressing to a more advanced stage. If we could find all the advanced precancerous lesions and take them out, that would be a huge public health home run.”

The recent development of blood-based colorectal cancer screening tests, which detect cancer markers in the blood, is a breakthrough that could benefit people hesitant to undergo stool-based screening or an invasive colonoscopy.

“The ability to detect markers of cancer in the blood at an actionable point is huge. These are mostly circulating DNA assays that are looking for particular alterations in the DNA, often methylation of specific DNA sequences but also DNA fragments or other changes. There’s interest in looking at anything that could be measured in the blood that could potentially correlate with the presence of cancer, including proteins.” 

The first approved blood-based colorectal cancer screening test has an 83% sensitivity rate for detecting colorectal cancer, but only a 13% sensitivity rate for detecting advanced precancerous polyps and a 57% sensitivity rate for early-stage colorectal cancer. Currently, colonoscopy and stool-based tests are much better at detecting advanced precancerous polyps, with colonoscopy being the most sensitive. Further, the available colorectal cancer blood-based screening test has a false positive rate of 10%, so patients who have a normal colon or non-advanced polyps test positive 10% of the time. 

“The positive rate in advanced precancerous polyps is almost the same as the false positive rate, so the tests aren’t really picking up these polyps. This is a big point of discussion.”

Ladabaum says that advanced precancerous polyps are not invasive, so unlike cancer, they may be less likely to cause circulating abnormalities in the blood. Scientists don’t yet know what blood marker could be associated with advanced precancerous polyps. 

He believes that, currently, blood-based tests are only suitable for average-risk patients who understand the tests are not as accurate as colonoscopy or stool-based tests and who do not wish or are unable to undergo the other tests. However, if blood-based tests get better at detecting advanced precancerous polyps and early-stage cancer, then it will be revolutionary in terms of the availability of screening options for patients, especially non-invasive options, and the future role of colonoscopy. Scientists will have to answer how often the tests should be performed to ensure the tests detect advanced polyps as they develop. 

“We think it takes many years for a polyp to develop into cancer, so we may get several shots at finding the polyp. If blood-based colorectal cancer screening tests prove to be a really good strategy that matches looking with colonoscopy every 10 years, then that’s a game changer.”

By Katie Shumake
March 2025