The American Cancer Society has released its first major update to colorectal cancer screening guidelines since 2018. The update comes after new molecular-based screening tests received FDA approval and as colorectal cancer rates continue to rise among younger adults.
Researchers have linked factors such as diet and environmental exposures to the increase in early-onset cases. Here are five key points from the updated guidelines.
Blood-based tests receive cautious recommendation
Liquid biopsy tests, also known as blood-based or cell-free DNA tests, are not recommended as preferred screening options at this time, according to the updated guidelines. These tests should only be offered to individuals who decline or have not completed a preferred screening test.
The main issue is sensitivity. Blood-based tests showed lower sensitivity for advanced precancerous lesions and stage I cancers compared with stool-based tests. This matters because the main goal of colorectal cancer screening is to prevent cancer 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 precancerous lesions. Blood-based tests showed very low sensitivity for advanced precancerous lesions, around 13% in two large studies.
Specificity also declines with age. In the ECLIPSE and PREEMPT CRC studies, specificity dropped from above 90% in participants younger than 55 to about 80% in those 70 and older. This means older adults face more false positives and greater risks from follow-up colonoscopy.
The guidelines note that blood-based tests have 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
Two newly approved stool tests have been added to the ACS’s preferred screening options list. ColoSense uses an algorithm combining eight RNA biomarkers, a fecal immunochemical test, and self-reported smoking status. 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 is an updated version of the original Cologuard test with a revised marker set. 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. They join a short list of recommended stool-based screening options that 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.
Medicare and Medicaid coverage for ColoSense is still pending as of the guideline update, which could affect access for some patients.
Positive non-colonoscopy tests require follow-up colonoscopy
Every non-colonoscopy screening test requires timely follow-up with colonoscopy if positive, preferably within 6 months. The guidelines state this is not optional and cannot be substituted with a repeat stool or blood test. Follow-up with a non-colonoscopy test after a positive result is not acceptable.
Real-world data suggest this is a genuine problem. Self-reported screening data are misleading partly because people who test positive on a non-colonoscopy test do not get their follow-up colonoscopies. One randomized trial 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.
Age-45 screening start recommendation stands
The ACS reaffirmed its 2018 recommendation to lower the recommended colorectal cancer screening start age from 50 to 45 for average-risk adults. Colorectal cancer incidence increased in adults younger than 50 at a rate of 3% per year between 2013 and 2022. Among US adults younger than 50, colorectal cancer is now the leading cause of cancer death among men and the second leading cause among women.
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 ACS-recommended screening. Screening rates were lower among Hispanic, Asian, and American Indian or Alaska Native individuals compared with White and Black individuals.
Disparities remain a serious concern
The guidelines note several differences in colorectal cancer burden by racial and ethnic group. Age-adjusted 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 have incidence rates 48% higher and mortality rates about 44% higher than White populations. Alaska Native people have more than double the incidence and mortality rates observed among White populations.
These disparities exist alongside gaps in screening access. Lack of insurance and lower socioeconomic status are associated with lower screening prevalence. The guidelines flag that the anticipated high cost of newer tests 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.
