What are the key updates in the 2026 ACS colorectal cancer screening guideline?

 COLORECTAL CANCER SCREENING UPDATE | CLINICAL PRACTICE SERIES

June 2026 | NP Chronicles Clinical Education

The ACS Just Updated Its Colorectal Cancer Screening Guideline. Here’s What NPs Need to Know.

By Valerie Watters-Burke, DNSc, MSN, MBA, FNP-BC, GNP-BC, PPCNP-BC

On stool-based molecular testing, blood-based screening, and why “the best test” is still the one the patient actually completes

CLINICAL AND PROFESSIONAL BOTTOM LINE

The 2026 American Cancer Society colorectal cancer screening guideline does not change the core age recommendations: average-risk adults should still begin screening at age 45, continue through age 75 if life expectancy is greater than 10 years, individualize screening decisions from ages 76 to 85, and generally stop screening after age 85.

What is new is the screening menu.

The ACS now recognizes newly approved molecular stool-based tests — including the multitarget stool RNA test and next-generation multitarget stool DNA test — as preferred stool-based screening options when used every 3 years. These join annual high-sensitivity FIT and high-sensitivity guaiac-based fecal occult blood testing as preferred noninvasive stool-based options.

Blood-based colorectal cancer screening also enters the conversation, but with important limits. The ACS does not consider blood-based cell-free DNA testing a preferred screening option at this time. It should be reserved for patients who decline or do not complete preferred stool-based testing or direct visual exams, and only after a clear conversation about its limitations — especially lower sensitivity for advanced precancerous lesions and early-stage cancers.

For NPs, the message is practical: offer options, explain trade-offs honestly, and make sure every positive noncolonoscopy test is followed by timely colonoscopy, preferably within 6 months. A stool test, blood test, or CT colonography is not “complete screening” if a positive result never gets diagnostic follow-up.

The Screening Conversation Is Changing

For years, colorectal cancer screening conversations have often sounded familiar:

“Are you ready for your colonoscopy?”

The patient hesitates.

Then the visit moves into the usual barriers: bowel prep, time off work, transportation, fear of sedation, insurance questions, embarrassment, prior bad experiences, or the simple reality that many patients do not want an invasive test unless they absolutely have to.

That conversation still matters. Colonoscopy remains a powerful screening and prevention tool because it can detect cancer and remove precancerous lesions in the same procedure. But the 2026 ACS update reflects what NPs already know from daily practice: patients do not all accept the same screening pathway.

Some patients will do a colonoscopy.

Some will complete a stool test at home.

Some will only agree to screening if it can be done with a blood draw.

And some will agree in the exam room but never complete the test unless the system follows up.

The ACS update is not just about adding new tests. It is about using the expanding screening landscape in a way that increases real completion — without quietly substituting less effective options for patients who would have completed a preferred test.

What Actually Changed in the 2026 ACS Guideline?

The biggest update is the addition of newer molecular-based stool tests and conditional guidance on blood-based testing.

The ACS now includes the multitarget stool RNA test, known as mt-sRNA, as a preferred stool-based option every 3 years. The guideline also addresses next-generation multitarget stool DNA testing, or ng-mt-sDNA, as an updated version of the already recommended stool DNA approach.

These tests are part of a broader shift toward molecular screening strategies that look for markers associated with colorectal cancer and advanced precancerous lesions. The goal is to improve detection while giving patients more acceptable noninvasive choices.

At the same time, the ACS is cautious about blood-based screening. Blood-based cell-free DNA testing may improve participation among people who otherwise remain unscreened, but it is not considered equivalent to preferred stool-based or visual screening options. The reason is important: blood-based tests have lower sensitivity for advanced precancerous lesions and stage I colorectal cancer compared with stool-based tests and direct visual exams.

That distinction matters clinically. Colorectal cancer screening is not only about finding cancer after it has developed. It is also about preventing cancer by identifying and removing advanced precancerous lesions before they become malignant.

Preferred Screening Options in 2026

For average-risk adults, the ACS continues to recommend regular screening with either a high-sensitivity stool-based test or a structural, direct visual examination.

Screening option	Recommended interval	Practical NP takeaway
High-sensitivity FIT	Every year	Strong option for programmatic screening, but only works if repeated annually and followed by colonoscopy when positive.
High-sensitivity gFOBT	Every year	Acceptable stool-based option, but dietary and medication restrictions can affect completion.
Multitarget stool DNA, original or next-generation	Every 3 years	Higher sensitivity for cancer and advanced precancerous lesions than FIT, but lower specificity, meaning more follow-up colonoscopies.
Multitarget stool RNA	Every 3 years	Newly added preferred stool-based option with high cancer sensitivity and moderate advanced lesion sensitivity, but lower specificity than some alternatives.
Colonoscopy	Every 10 years	Direct visualization and polyp removal; requires bowel prep, time, transportation, and procedural access.
CT colonography	Every 5 years	Visual exam option; positive findings still require colonoscopy.
Flexible sigmoidoscopy	Every 5 years	Less commonly used and does not evaluate the full colon.

The key clinical point: more options can increase screening participation, but only if patients understand what each option can and cannot do.

The New Stool RNA Test: What NPs Should Know

The multitarget stool RNA test is one of the most important additions in the 2026 update.

Unlike a traditional stool blood test alone, mt-sRNA combines multiple RNA biomarkers with a FIT component and patient-reported smoking status to generate a screening result. In the evidence reviewed by the ACS, mt-sRNA demonstrated high sensitivity for colorectal cancer and moderate sensitivity for advanced precancerous lesions.

That sounds promising — and it is — but it comes with a trade-off.

Compared with FIT, mt-sRNA may detect more cancers and advanced lesions in a single round of testing, but it has lower specificity. Lower specificity means more false positives, which means more patients will be referred for colonoscopy after a positive test even though cancer or advanced precancerous lesions may not ultimately be found.

That does not make the test “bad.” It means the NP needs to frame it accurately.

A patient choosing mt-sRNA should understand:

·       It is done at home.

·       It is recommended every 3 years.

·       A positive result must be followed by colonoscopy.

·       It may lead to more follow-up colonoscopies than FIT because of lower specificity.

·       Long-term real-world adherence and repeated-round performance will need continued monitoring.

This is where NPs are essential. The test itself does not create a screening program. Patient education, tracking, follow-up, and colonoscopy completion do.

Blood-Based Screening: Useful, But Not Preferred

Blood-based colorectal cancer screening is likely to generate patient interest. Many patients who have avoided stool testing or colonoscopy may be willing to say yes to a blood draw.

That is the opportunity.

But the ACS is clear that blood-based testing should not be presented as simply equivalent to preferred screening options.

Blood-based cell-free DNA tests have lower sensitivity for advanced precancerous lesions and stage I colorectal cancer. That matters because a screening test that misses more early disease and more precancerous lesions has less potential to reduce colorectal cancer incidence and mortality.

In plain language: a blood test may be better than no screening, but it is not better than completing a preferred screening option.

The ACS recommends blood-based screening only for individuals who decline or do not complete preferred colorectal cancer screening tests. It should not be ordered casually, automatically, or without prior discussion.

A useful NP framing might be:

“If you are willing to complete a stool-based test or colonoscopy, those are preferred options because they are better at detecting precancerous changes and early cancer. If you are not willing or able to complete those, a blood-based test may still be better than remaining unscreened — but we need to talk through what it can miss and what happens if it is positive.”

That conversation preserves patient autonomy without overstating the test.

The Age Recommendations Did Not Change

Despite the addition of new testing options, the age framework remains the same.

The ACS continues to recommend that average-risk adults begin colorectal cancer screening at age 45. Screening should continue through age 75 for adults in good health with a life expectancy greater than 10 years.

From ages 76 through 85, screening decisions should be individualized. That means NPs should consider the patient’s overall health, life expectancy, prior screening history, personal preferences, and whether the patient would be able and willing to complete follow-up colonoscopy or treatment if something is found.

After age 85, colorectal cancer screening is generally discouraged.

This age framework is especially important because colorectal cancer rates have been rising among younger adults. The 45-year starting point is not an administrative detail. It is a clinical response to a real epidemiologic shift.

A Positive Noncolonoscopy Test Is Not the End of Screening

This may be the most important operational point in the entire guideline.

Every positive noncolonoscopy screening test requires timely follow-up colonoscopy to complete the screening process. That includes FIT, gFOBT, mt-sDNA, mt-sRNA, CT colonography, flexible sigmoidoscopy findings requiring full evaluation, and blood-based tests.

A positive stool or blood test without colonoscopy is an unfinished screening episode.

The ACS emphasizes follow-up preferably within 6 months. Delays matter because the purpose of screening is not simply to generate a lab result. The purpose is to identify disease early enough to prevent cancer or reduce mortality.

For practices, this means screening cannot be treated as a “hand the patient a kit and hope” process.

A reliable colorectal cancer screening workflow should include:

1.      Identifying eligible patients beginning at age 45.

2.      Offering preferred screening options with clear counseling.

3.      Documenting the patient’s chosen screening method.

4.      Tracking whether the test was completed.

5.      Contacting patients who do not return stool kits or complete ordered tests.

6.      Flagging every positive result.

7.      Coordinating timely colonoscopy.

8.      Confirming colonoscopy completion and pathology follow-up.

9.      Returning the patient to the appropriate screening or surveillance interval.

Without that infrastructure, even the best test underperforms.

What NPs Should Say in Practice

Patients do not need a lecture on molecular assays. They need a clear recommendation and a practical choice.

For an average-risk 46-year-old who has never been screened:

“You are now in the age range where colorectal cancer screening is recommended. We have several options, including stool-based tests you can do at home and colonoscopy. The most important thing is choosing a high-quality option you will actually complete.”

For a patient avoiding colonoscopy:

“Colonoscopy is one option, but it is not the only option. If you are not ready for that, we can talk about stool-based screening. Some are done every year, and some molecular stool tests are done every 3 years. If any of them are positive, the next step is colonoscopy.”

For a patient asking for the blood test:

“There is a blood-based screening test, but it is not the preferred option because it is less sensitive for precancerous lesions and early cancers. If you are willing to do a stool test or colonoscopy, those are better choices. If you are not willing to do those, then we can discuss the blood test as an alternative to remaining unscreened.”

For a patient with a positive stool or blood test:

“This result does not mean you have cancer, but it does mean we need to complete the screening process with a colonoscopy. The follow-up colonoscopy is the step that tells us what is actually going on.”

The Real Clinical Challenge Is Completion

The 2026 ACS update gives NPs more tools. But more tools do not automatically produce better outcomes.

A patient can be offered the perfect screening option and still never complete it.

A stool kit can sit on the kitchen counter.

A colonoscopy referral can get lost between scheduling calls, insurance questions, and transportation barriers.

A positive test can be documented in the chart without anyone owning the next step.

That is where nursing practice matters.

NPs are often the clinicians who identify the overdue patient, explain the why, troubleshoot the barrier, and reinforce follow-through. The guideline update should push practices to think beyond “screening ordered” and toward “screening completed.”

Final Clinical Bottom Line

The 2026 ACS colorectal cancer screening guideline expands preferred stool-based screening options to include newer molecular tests such as multitarget stool RNA and next-generation multitarget stool DNA testing at 3-year intervals. It also introduces cautious, conditional guidance for blood-based screening, limiting its use to patients who decline or fail to complete preferred stool-based or visual screening options.

The core recommendations remain unchanged: start average-risk screening at age 45, continue through age 75 when life expectancy supports it, individualize from 76 to 85, and discourage screening after 85.

For NPs, the practical message is straightforward: offer patients real choices, explain the trade-offs clearly, do not oversell blood-based screening, and build reliable systems to ensure positive noncolonoscopy tests are followed by colonoscopy.

Because the best colorectal cancer screening test is not the newest test, the easiest test, or the one ordered most often.

It is the one the patient completes — and the one the practice follows all the way through.

 

References

1. Wolf AMD, Hoffman RM, Walter LC, Zeigler-Johnson C, Church TR, Guerra CE, Elkin EB, Etzioni R, Herzig A, Oeffinger KC, Perkins RB, Raoof S, Shih Y-CT, Skates SJ, Kratzer TB, Manassaram-Baptiste D, Smith RA. Colorectal cancer screening: An update to the American Cancer Society guideline, 2026. CA: A Cancer Journal for Clinicians. 2026. doi:10.3322/caac.70083.
2. American Cancer Society. Colorectal Cancer Screening Guidelines. American Cancer Society. Accessed June 2026.
3. U.S. Food and Drug Administration. FDA approves new colorectal cancer screening tests, including molecular stool-based and blood-based screening options. U.S. Food and Drug Administration. Accessed June 2026.
4. Centers for Medicare & Medicaid Services. Medicare coverage information for colorectal cancer screening tests. Centers for Medicare & Medicaid Services. Accessed June 2026.

 

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This post is intended for educational purposes. Always consult the full prescribing information and current clinical guidelines for patient care decisions.