ACS Expands CRC Screening Guidelines With New Blood-Based, Stool Tests

New colorectal cancer (CRC) screening guidelines from the American Cancer Society (ACS) add a blood-based test and a novel stool RNA option alongside an updated stool DNA test, aiming to expand options and reduce the more than 20 million unscreened Americans, according to a report published today in CA: A Cancer Journal for Clinicians.¹

What Changed, What Remains the Same

The updated ACS guideline adds 3 tests to its recommended screening options, reflecting advances in disease detection and a broader public health effort to expand access and lower barriers to screening.

Two are multitarget stool-based options: a next-generation multitarget stool DNA test, marketed as Cologuard, that analyzes stool for specific DNA markers and hemoglobin; and a new multitarget stool RNA test, marketed as ColoSense, that detects RNA markers and hemoglobin. Both carry a 3-year testing interval and demonstrate high sensitivity for CRC, with moderate sensitivity for advanced precancerous lesions.

The third addition is a blood-based test called Shield that detects circulating tumor DNA. The ACS recommends it only for individuals who decline or fail to complete preferred stool-based or visual screening. Compared with established stool tests, blood-based tests show lower sensitivity for both early-stage cancers and advanced precancerous lesions, with modeling suggesting it may be less effective in reducing CRC incidence and mortality.

A positive result from any stool- or blood-based test requires a timely follow-up colonoscopy, preferably within 6 months, to complete the screening process.

Meanwhile, the core age recommendation holds firm: average-risk adults should begin screening at 45 and continue through age 75; individuals potentially need to start earlier depending on their family cancer history. Recommended every 10 years, colonoscopy also remains the key screening option. Other unchanged options include annual high-sensitivity guaiac-based fecal occult blood tests and fecal immunochemical tests, flexible sigmoidoscopy every 5 years, and CT colonography every 5 years.

“By offering more screening tools in our guideline update, more eligible adults will be able to participate in lifesaving CRC testing, helping to close the screening gap and catch more cancers at an earlier, treatable stage,” Robert Smith, PhD, senior author of the report and senior vice president of early cancer detection science at the ACS, said in a news release.

The ACS Guideline Development Group will continue monitoring adherence, real-world implementation, and clinical outcomes to inform future updates.

Rising CRC Burden Highlights Need for Updated Guidance

The update carries particular importance as CRC incidence and mortality continue rising among adults younger than 65.² The ACS “Colorectal Cancer Statistics, 2026” report found CRC incidence increasing by 3% per year among patients aged 20 to 49 years and 0.4% among those aged 50 to 64 years, with 45% of new cases now occurring in these younger age groups.

Mortality is also rising among younger adults, with individuals younger than 50 years experiencing a 1% annual increase since 2004, and those aged 50 to 64 years seeing a 1.2% annual increase from 2019 to 2023.

Rebecca L. Siegel, MPH, senior scientific director of surveillance research at ACS, underscored the importance of clinicians recognizing this shift in an interview with The American Journal of Managed Care^® (AJMC^®).

“Twenty years ago, it was people in their 70s being treated,” she said. “Now, it's people much younger… so really understanding that you are treating a different patient with unique needs, giving more information about treatment options and side effects of those treatments, like sexual dysfunction and infertility…it’s important for clinicians to understand this pain and make changes in their practice that address these younger patients.”

Screening Gaps, Prevention Priorities

Jordan Karlitz, MD, emphasized that the increase in CRC-related deaths in patients younger than 50 is partly due to delayed or missed screening in an interview with AJMC. Karlitz is the senior medical officer of screening at Exact Sciences and holds a voluntary teaching position at the University of Colorado School of Medicine; he previously served as chief of the gastroenterology and hepatology division at Denver Health Medical Center.

Screening uptake varies considerably by population, with lower rates among recent immigrants, uninsured patients, and less-educated individuals, according to the "Colorectal Cancer Statistics, 2026" report. Overall, state screening rates range from approximately 59% to 78%.

Amid the changing CRC landscape, Karlitz outlined 3 pillars for prevention and early detection: getting screened on time, knowing your family cancer history, and acting promptly on symptoms.

“These are the 3 pillars that everybody needs to be aware of, whether you’re a community member, a health care provider, or working in another role, because I think gaps in any of them could increase the risk of developing CRC and, unfortunately, lead to presenting with more advanced-stage disease,” he told AJMC.

References

1. American Cancer Society updates colorectal cancer screening guideline: major changes emphasize blood-based and at-home stool testing. News release. ACS. May 27, 2026. Accessed May 27, 2026. https://pressroom.cancer.org/colorectal-cancer-screening-guideline-update-2026
2. McCormick B. 2026 ACS report shows CRC rising in younger adults despite overall decline. AJMC. March 3, 2026. Accessed May 27, 2026. https://www.ajmc.com/view/2026-acs-report-shows-crc-rising-in-younger-adults-despite-overall-decline