The American Cancer Society has released its first major update to colorectal cancer screening guidelines since 2018. The update comes after the arrival of 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. The following are five key points from the updated guidelines.
Blood-based tests receive cautious recommendation
Blood-based tests, also known as liquid biopsy or cell-free DNA tests, are not recommended as preferred screening options at this time, according to the 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 detecting and removing precancerous lesions. One modeling study cited in the guidelines estimated that 80% of the long-term mortality benefit from screening comes from detecting these lesions. Blood-based tests have very low sensitivity for advanced precancerous lesions, around 13% in two large studies. Specificity also declines with age, dropping 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. However, the guidelines acknowledge that blood-based tests have value for people who would otherwise not get screened at all.
Two new stool-based tests added to preferred list
Two newly approved stool tests have been added to the preferred screening options list. ColoSense uses an algorithm combining eight RNA biomarkers, a fecal immunochemical test, and self-reported smoking status. In a 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 to improve specificity. In a study, it showed 93.9% sensitivity for colorectal cancer and 43.4% sensitivity for advanced precancerous lesions. It also received FDA approval in 2024. Both tests are done every three years. Modeling studies suggest these options offer a similar ability to reduce colorectal cancer cases and mortality as other recommended stool-based tests. Medicare and Medicaid coverage for ColoSense is still pending as of the guideline update, which could affect access for some patients.
Positive non-colonoscopy test requires follow-up colonoscopy
Every non-colonoscopy screening test, whether stool-based or blood-based, requires timely follow-up with a colonoscopy if positive. The guidelines state this should happen within six months. A positive result cannot be followed up with a repeat stool or blood test. Real-world data show this is a problem. The guidelines note that self-reported screening data are misleading because many people who test positive on a non-colonoscopy test do not get their follow-up colonoscopy. 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 six months, compared with 70% of those with a positive fecal test.
Age 45 screening start recommendation remains
The 2018 recommendation to lower the recommended screening start age from 50 to 45 for average-risk adults is reaffirmed. 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 recommended screening.
Disparities remain a serious concern
Colorectal cancer burden varies by racial and ethnic group. Age-adjusted incidence rates are estimated to be 11% higher among Black individuals, and 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 also flag that the anticipated high cost of newer tests, including blood-based tests, ColoSense, and Cologuard Plus, will be 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. The guidelines frame the inclusion of additional screening modalities as part of a commitment to equity, with more options meaning more opportunities to reach different populations.
