The American Cancer Society has released its first major update to colorectal cancer screening guidelines since 2018. The update was prompted by two developments: new molecular-based screening tests that received FDA approval, and persistent increases in colorectal cancer rates among younger adults. Researchers have linked factors such as diet and environmental exposures to the rise in early-onset cases, making updated screening guidance more pressing. Below are five key points from the updated guidelines.
Blood-based tests get a cautious thumbs-down
Liquid biopsy tests, also known as blood-based or cell-free DNA tests, have been promoted as a convenient alternative to stool tests and colonoscopies. However, the American Cancer Society is not endorsing them as a preferred option. According to the updated guidelines, blood-based tests are not recommended as preferred screening choices at this time. They should only be offered to individuals who decline or have not completed a preferred screening test.
The main issue is sensitivity. Blood-based tests show lower sensitivity for advanced precancerous lesions and stage I cancers compared with established stool-based tests. This matters because the primary goal of colorectal cancer screening is not just to detect cancer, but to prevent it by finding and removing precancerous lesions before they become cancer. One modeling study cited in the guidelines estimated that 80% of the long-term mortality benefit from screening comes from detecting and removing these lesions. Blood-based tests have very low sensitivity for advanced precancerous lesions, around 13% in two large prospective studies, falling short of that goal.
There is also a problem with declining specificity as people age. In the ECLIPSE and PREEMPT CRC studies, specificity dropped from above 90% in participants under 55 to about 80% in those 70 and older. This means older adults face more false positives, along with the greatest risks from follow-up colonoscopy. Still, the American Cancer Society acknowledges that blood-based tests have value for people who would otherwise go unscreened. For them, a blood-based test is better than nothing.
Two new stool-based tests are now preferred
The most significant update in the new guidelines is the addition of two newly approved stool tests to the preferred screening options list. ColoSense, also known as mt-sRNA, uses an algorithm combining eight RNA biomarkers, a fecal immunochemical test, and self-reported smoking status to identify individuals at higher risk for abnormal growths in the large intestine. In the CRC-PREVENT validation study, it showed 94.4% sensitivity for colorectal cancer, 100% sensitivity for stage I disease, and 45.9% sensitivity for advanced adenoma. It received FDA approval in 2024.
Cologuard Plus, also known as ng-mt-sDNA, is an updated version of the original Cologuard test with a revised marker set designed to improve specificity while maintaining high sensitivity. In the BLUE-C study, it showed 93.9% sensitivity for colorectal cancer and 43.4% sensitivity for advanced precancerous lesions, with improved specificity compared to the original test. It also received FDA approval in 2024. Both tests are done every three years and join a short list of recommended stool-based screening options, which also includes annual high-sensitivity stool blood tests and an older DNA stool test. Modeling studies suggest all these options offer a similar ability to reduce colorectal cancer cases and mortality. Medicare and Medicaid coverage for ColoSense is still pending as of the time of this update, which could affect access for some patients.
A positive non-colonoscopy test always requires follow-up colonoscopy
This point applies to every non-colonoscopy screening test, stool-based and blood-based alike. The guidelines are clear that a positive result requires timely follow-up with colonoscopy, preferably within 6 months, to complete the screening process. This is not optional, and it cannot be substituted with a repeat stool or blood test. The guidelines explicitly state that follow-up with a non-colonoscopy test after a positive result is not acceptable.
Real-world data suggest this is a genuine problem. The guidelines note that self-reported screening data are misleading in part because people who test positive on a non-colonoscopy screening test do not get their follow-up colonoscopies. Data from one randomized trial cited in the guidelines showed that only 50% of participants with a positive blood-based test completed a follow-up colonoscopy within 6 months, compared with 70% of those with a positive fecal test. A positive screening test is the beginning of the process, not the end.
The age-45 screening start recommendation stands
In 2018, the American Cancer Society made a landmark decision to lower the recommended colorectal cancer screening start age from 50 to 45 for average-risk adults. That recommendation is reaffirmed in this update. The rationale has not changed, and the data have become more urgent. Colorectal cancer incidence increased in adults younger than 50 at a rate of 3% per year between 2013 and 2022. Among U.S. adults younger than 50, colorectal cancer is now the leading cause of cancer death among men and the second leading cause among women. Research has implicated diet as a key driver of this trend, particularly in women under 50.
Despite the 2018 recommendation, uptake among the newly eligible age group remains low. In 2023, only 37% of adults aged 45 to 49 reported being up to date with American Cancer Society-recommended colorectal cancer screening. The guidelines also note that screening rates were lower among Hispanic individuals at 56%, Asian individuals at 58%, and American Indian or Alaska Native individuals at 59%, compared with White individuals at 67% and Black individuals at 66%.
Disparities remain a serious and urgent concern
These inequities in screening uptake are not the only differences by racial and ethnic group. The guidelines mention several stark differences in colorectal cancer burden. Age-adjusted incidence rates are estimated to be 11% higher among Black individuals, and their mortality rates are about 40% higher than White individuals. Among American Indian and Alaska Native populations, incidence rates are 48% higher and mortality rates are about 44% higher than White populations. Alaska Native people specifically have more than double the colorectal cancer incidence and mortality rates observed among White populations in the United States.
These disparities exist alongside persistent gaps in screening access. Lack of insurance and lower socioeconomic status are associated with lower screening prevalence. The guidelines also flag that the anticipated high cost of newer tests, including blood-based tests, ColoSense, and Cologuard Plus, will represent a significant barrier for uninsured and underinsured populations. Annual high-sensitivity stool blood tests and older DNA stool tests remain the low-cost options among recommended tests. Modifiable lifestyle factors like alcohol consumption also contribute to colorectal cancer risk and are worth addressing alongside screening efforts. The American Cancer Society frames the inclusion of additional screening modalities as part of its commitment to equity, saying more options means more opportunities to reach people who might otherwise go unscreened.
