In July 2026, the U.S. Food and Drug Administration approved a second blood-based screening test for colorectal cancer, expanding the options available to average-risk adults who have been skipping traditional exams. The approval of Freenome’s SimpleScreen CRC follows the 2024 clearance of Guardant Health’s Shield test and comes at a moment when roughly 60 million eligible U.S. adults remain unscreened, according to public health data.
Colorectal cancer is the second leading cause of cancer death worldwide and the second-deadliest cancer in the United States when men and women are combined, per the American Cancer Society. Screening dramatically reduces mortality — yet a large share of those eligible never complete a colonoscopy or stool test. Researchers hope a simple blood draw at a routine office visit will help close that gap.
How the New Blood Test Works
SimpleScreen CRC analyzes patterns of DNA methylation — chemical modifications to cytosine-phosphate-guanine (CpG) sites that shift early during tumor development. Cancer cells shed fragments of altered DNA into the bloodstream, and the test looks for the methylation signatures characteristic of colorectal tumors. A single tube of blood is drawn at a healthcare provider’s office, and results typically return within about two weeks.
The pivotal PREEMPT CRC study, published in the New England Journal of Medicine in 2025 and cited in the FDA’s review, enrolled more than 48,000 adults across the United States and Europe. In that trial, the assay identified colorectal cancer with roughly 80% sensitivity and returned negative results in about 90% of participants without cancer or advanced precancerous lesions — a measure known as specificity.
Comparing SimpleScreen CRC and Shield
Guardant Health’s Shield test, the first blood-based colorectal cancer screen approved by the FDA in July 2024, reported similar performance in its ECLIPSE study: 83% sensitivity for colorectal cancer and 90% specificity. Both tests share a critical limitation — sensitivity for advanced precancerous adenomas (large polyps that can be removed before they turn malignant) hovers around 13% to 15%, far below the roughly 40% to 45% seen with stool DNA tests like Cologuard, according to trial data summarized by the National Cancer Institute.
Where Blood Tests Fit in the Screening Landscape
Guidelines from the U.S. Preventive Services Task Force recommend colorectal cancer screening for average-risk adults starting at age 45 and continuing through age 75, with selective screening for those aged 76 to 85 based on individual health. As of the task force’s most recent update, blood tests are not among the endorsed first-line options; the panel cited limited long-term evidence on outcomes such as mortality reduction. The American Cancer Society takes a slightly more permissive view, listing blood-based tests as an option for people who decline the preferred alternatives.
Colonoscopy Remains the Reference Standard
Colonoscopy is the only screening method that both detects colorectal cancer and removes precancerous polyps in the same procedure. Meta-analyses in journals including The Lancet and the New England Journal of Medicine associate the exam with substantial reductions in colorectal cancer incidence and mortality when performed every 10 years in average-risk adults. Its downside is preparation, sedation, and the small but real risks of bleeding or perforation.
Stool-Based Tests
Stool tests fill the middle of the screening pyramid. The fecal immunochemical test (FIT), performed annually, detects hidden blood in a small stool sample and has a sensitivity for colorectal cancer of roughly 74%, according to a 2019 Annals of Internal Medicine review. Multitarget stool DNA tests such as Cologuard, done every one to three years, add DNA marker analysis and improve sensitivity for cancer to around 92% and for advanced adenomas to about 42%. Both are performed at home and returned by mail.
Who Might Consider a Blood Test
Research suggests blood-based screening is best positioned as an engagement tool, not a replacement for colonoscopy or stool testing. Studies published in JAMA Network Open indicate that offering a blood test to previously unscreened adults can raise screening participation rates, and modeling analyses from the National Cancer Institute project a mortality benefit when a blood test convinces someone who would otherwise decline all screening to participate.
Clinicians commonly discuss blood-based screening with patients who:
- Have repeatedly declined a colonoscopy or a stool-based test
- Face access barriers to colonoscopy, such as transportation, time off work, or lack of a chaperone for sedation
- Are between ages 45 and 75, at average risk, and have no personal or family history of colorectal cancer, inflammatory bowel disease, or hereditary cancer syndromes
Anyone with a family history, prior polyps, symptoms such as rectal bleeding or unexplained anemia, or genetic risk factors is typically directed to colonoscopy rather than a blood test.
The Trade-Offs
A positive blood test result is not a diagnosis — it triggers a follow-up colonoscopy to determine whether cancer or a precancerous lesion is present. False positives can generate anxiety and additional procedures, while false negatives may offer misplaced reassurance. Because blood tests miss most advanced polyps, they are less effective than colonoscopy or stool DNA tests at preventing cancer, as opposed to detecting it after it has already formed.
Coverage and cost also vary. Medicare covers blood-based colorectal cancer screening every three years for eligible beneficiaries under a National Coverage Determination finalized after Shield’s approval; commercial insurance coverage is still expanding as of 2026.
Early-Onset Colorectal Cancer
Rates of colorectal cancer among adults under 50 have risen steadily since the mid-1990s, prompting the USPSTF to lower the recommended screening start age from 50 to 45 in 2021. A 2024 JAMA analysis found early-onset colorectal cancer incidence rising by roughly 2% per year among adults aged 20 to 49. Researchers continue to investigate contributing factors including diet, obesity, gut microbiome shifts, and environmental exposures, but a definitive cause has not been established.
The Bottom Line
The FDA’s approval of a second blood test signals growing regulatory confidence in liquid biopsy screening — and gives patients and clinicians another way to start a screening conversation. But experts consistently note that no screening test benefits anyone unless it is actually completed, and every abnormal result still leads back to a colonoscopy. For most average-risk adults, discussing the full range of options with a primary care provider remains the most reliable path to catching colorectal cancer early or preventing it entirely.
Disclosure: This content is for informational purposes only and is not medical advice. Always consult a qualified healthcare provider before making changes to your health regimen.