The American Cancer Society just released its first major update to colorectal cancer (CRC) screening guidelines since 2018, and there’s a lot to unpack. The update was prompted by two developments: the arrival of new molecular-based screening tests that have received FDA regulatory approval, and persistently worrying trends in CRC rates among younger adults.
Blood-based tests get a cautious thumbs-down
Liquid biopsy tests, also known as blood-based or cell-free DNA tests, have generated a lot of buzz as a convenient alternative to stool tests and colonoscopies. But the ACS is pumping the brakes.
According to the updated guidelines, blood-based tests are not recommended as preferred screening options at this time. They should only be offered to individuals who decline or have not completed a preferred CRC screening test.
The core problem with these tests is sensitivity. The blood-based tests demonstrated lower sensitivity for both advanced precancerous lesions (APLs) and stage I cancers compared with established stool-based tests. That distinction matters enormously because the principal goal of CRC screening isn’t just to detect cancer. It’s to prevent it by catching and removing precancerous lesions before they become cancer.
According to the guidelines, one modeling study estimated that 80% of the long-term CRC mortality benefit from screening comes from detecting and removing precancerous lesions. Blood-based tests, with their very low sensitivity for APLs (around 13% in two large prospective studies), fall well short of that goal.
There’s also the issue of declining specificity with age. In both the ECLIPSE and PREEMPT CRC studies, specificity dropped from above 90% in participants younger than 55 to about 80% in those 70 and older, which means older adults are faced with more false positives, in addition to the greatest risks from follow-up colonoscopy.
That being said, the ACS acknowledges that blood-based tests have real value for people who would otherwise go unscreened entirely. For them, a blood-based test is better than nothing.
Two new stool-based tests are now “preferred”
This is the most significant update in the new guidelines. Two newly approved stool tests have been added to the ACS’s preferred screening options list:
ColoSense (mt-sRNA): The multitarget stool test uses an algorithm combining eight RNA biomarkers, a fecal immunochemical test (FIT), and self-reported smoking status to identify individuals at higher risk for any abnormal growth of cells in the large intestine. In the CRC-PREVENT validation study, it showed 94.4% sensitivity for CRC, 100% sensitivity for stage I disease, and 45.9% sensitivity for advanced adenoma. It received FDA approval in 2024.
Cologuard Plus (ng-mt-sDNA): The next-generation multitarget stool DNA test 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 CRC and 43.4% sensitivity for APL, 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 of these options offer a similar ability to reduce colorectal cancer cases and mortality.
It’s also worth noting that Medicare & Medicaid coverage for ColoSense is still pending as of the time of this guideline 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, and the guidelines are unambiguous about it. A positive result requires timely follow-up with colonoscopy, preferably within 6 months, to complete the screening process.
This is not optional, and it’s not something that can 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.
Why does this need to be said? Because real-world data suggest it’s 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 don’t 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.
So remember, a positive screening test is the beginning of the process, not the end.
The age-45 screening start recommendation stands
In 2018, the ACS made a landmark decision to lower the recommended CRC screening start age from 50 to 45 for average-risk adults. That recommendation is reaffirmed in this update.
The rationale hasn’t changed. If anything, the data have become more urgent. CRC incidence increased in adults younger than 50 at a rate of 3% per year between 2013 to 2022. Among US adults younger than 50, CRC 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 45–49 reported being up to date with ACS-recommended CRC screening. The guidelines also note that screening rates were lower among Hispanic (56%), Asian (58%), and American Indian or Alaska Native (59%) individuals compared with White (67%) and Black (66%) individuals.
Disparities remain a serious and urgent concern
These inequities in earlier colon cancer screening uptake are not the only thing that differs by racial and ethnic group. The guidelines mention several stark differences in CRC burden:
Black individuals: Age-adjusted CRC incidence rates are estimated to be 11% higher among Black individuals, and their mortality rates are about 40% higher than White individuals.
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 CRC 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 CRC risk and are worth addressing alongside screening efforts.
The ACS frames the inclusion of additional screening modalities as part of its commitment to equity. More options means more opportunities to reach people who face barriers to colonoscopy or stool-based testing. But the guidelines are clear that expanding options alone isn’t enough without parallel efforts to ensure equitable access and coverage.
The bottom line
The 2026 ACS guideline update refines CRC screening guidelines from 2018. The core message remains the same: get screened starting at 45, stick with a preferred test, and if that test comes back positive, follow up with a colonoscopy.
If you’re 45 or older and haven’t been screened, the most important takeaway is to talk to your doctor about which test is right for you. The best screening test, as the guidelines put it, is the one that you actually complete.
