ColoSense vs Cologuard: Which Stool Test Is Better for Colorectal Cancer Screening in 2026?

"Compare ColoSense and Cologuard Plus accuracy, screening methods, and Medicare coverage."

Illustration. A doctor explains cancer examination and treatment to a patient at a hospital.

For adults looking for a colorectal cancer screening option they can complete at home, stool-based tests have become an important alternative to starting with colonoscopy.

In 2026, two names stand out: ColoSense and Cologuard.

But there is an important update for patients comparing these tests.

The current next-generation Cologuard test is Cologuard Plus, while ColoSense is a newer multi-target stool RNA (mt-sRNA) test.

Both are noninvasive stool-based screening tests for adults at average risk of colorectal cancer. Both are designed to detect biological signals associated with colorectal cancer and precancerous lesions. And a positive result from either test requires follow-up colonoscopy.

The biggest difference is what the tests look for.

Cologuard Plus uses DNA methylation markers and hemoglobin.

ColoSense uses RNA biomarkers and hemoglobin.

The tests also have different clinical-study performance results, and those results should not be interpreted as a simple head-to-head contest because the pivotal studies were conducted separately.

So which test is better?

There is no universal winner.

For many average-risk adults, the most important question is which recommended screening test they are willing and able to complete consistently.

Medical information: This article is for educational purposes only and does not replace professional medical advice. Screening decisions should be based on age, risk factors, medical history, symptoms, previous screening results and discussion with a healthcare professional.

What Is ColoSense?

ColoSense is an FDA-approved, noninvasive stool-based colorectal cancer screening test developed by Geneoscopy.

The FDA approved ColoSense in May 2024.

Unlike traditional stool blood tests that primarily look for blood, ColoSense analyzes eight RNA biomarkers along with hemoglobin in stool.

The test is performed using a stool sample collected at home and sent to a laboratory for analysis.

The FDA indication is for adults 45 years and older who are at average risk for colorectal cancer.

ColoSense is not intended to replace diagnostic colonoscopy or surveillance colonoscopy for people at high risk.

A positive ColoSense result should be followed by colonoscopy.

A negative result also does not guarantee that colorectal cancer or an advanced precancerous lesion is absent.

What Is Cologuard?

Cologuard is the established brand of multi-target stool DNA colorectal cancer screening.

In 2026, the newer version is Cologuard Plus.

Cologuard Plus is an FDA-approved stool-based screening test that analyzes DNA methylation markers and hemoglobin.

Like ColoSense, it is intended for adults age 45 and older who are at average risk for colorectal cancer.

A positive Cologuard Plus result should be followed by colonoscopy.

It is important not to confuse the original Cologuard test with Cologuard Plus when comparing current 2026 performance data.

The two are related products, but their FDA clinical data are not identical.

ColoSense vs Cologuard: What Is the Main Difference?

The simplest difference is the type of molecular signal each test analyzes.

The molecular technology is different, but the practical screening pathway is similar:

At-home stool test → positive or negative result → colonoscopy if positive.

What Does ColoSense Look For?

ColoSense analyzes RNA markers associated with colorectal neoplasia.

The FDA describes the test as detecting colorectal-neoplasia-associated RNA markers and occult hemoglobin in stool.

The test uses eight RNA biomarkers.

RNA can reflect changes in gene activity associated with abnormal or cancerous tissue.

The test's algorithm combines the biomarker information with hemoglobin and smoking status to produce a positive or negative screening result.

The important point for patients is that ColoSense is not simply a stool blood test.

It is a molecular stool test designed to identify signals associated with colorectal cancer and certain precancerous lesions.

What Does Cologuard Plus Look For?

Cologuard Plus analyzes DNA methylation markers and hemoglobin.

DNA methylation refers to chemical changes that can alter gene activity without changing the underlying DNA sequence.

Certain methylation patterns can be associated with colorectal neoplasia.

Cologuard Plus combines these molecular signals with hemoglobin detection to generate the screening result.

Like ColoSense, it is intended to identify people who should undergo additional evaluation rather than directly diagnose cancer.

How Accurate Is ColoSense?

FDA clinical-study data provide several important performance measures.

In the pivotal average-risk clinical cohort, ColoSense had:

• 92.6% sensitivity for colorectal cancer

• 41.3% sensitivity for advanced adenomas or serrated precancerous lesions

• 85.6% specificity for negative findings in the primary performance category

The study included 7,763 participants in the average-risk clinical effectiveness population.

The FDA also reported sensitivity of:

• 44.9% for advanced adenomas;

• 22.4% for serrated precancerous lesions;

• and 87.5% specificity among people with no lesions on colonoscopy.

These numbers describe performance in the clinical-study population.

They should not be interpreted as a guarantee that ColoSense will detect or exclude cancer in an individual patient.

How Accurate Is Cologuard Plus?

The FDA's pivotal BLUE-C study evaluated 18,911 participants in the primary effectiveness population.

The study reported:

• 95.3% sensitivity for colorectal cancer

• 43.3% sensitivity for advanced precancerous lesions

• 90.7% specificity for the primary negative category

For participants with no colorectal neoplasia, specificity was 92.7%.

The FDA also reported a positive predictive value of 3.2% for colorectal cancer and 34.0% for advanced precancerous lesions in the study population.

Again, these are clinical-study results.

They are not the same thing as an individual's personal probability of having cancer after a positive result.

Is Cologuard Plus More Accurate Than ColoSense?

It would be tempting to look at the numbers and declare Cologuard Plus the winner.

That would be too simplistic.

The published FDA performance numbers come from different pivotal studies with different study populations and designs.

ColoSense reported 92.6% sensitivity for colorectal cancer and 85.6% specificity for its primary negative category.

Cologuard Plus reported 95.3% sensitivity for colorectal cancer and 90.7% specificity for its primary negative category.

Those numbers cannot be treated as a randomized head-to-head comparison.

A direct comparison would require both tests to be evaluated in the same appropriately designed population under the same conditions.

Therefore, it is more accurate to say:

Both tests have FDA-reviewed evidence supporting their use as noninvasive colorectal cancer screening tests, but their published performance numbers come from separate studies.

Which Test Detects More Colorectal Cancer?

In their respective FDA pivotal studies:

ColoSense: 92.6% colorectal cancer sensitivity.

Cologuard Plus: 95.3% colorectal cancer sensitivity.

That means Cologuard Plus had the higher point estimate in its pivotal study.

But this does not prove that Cologuard Plus will detect more cancers than ColoSense in every real-world population.

Differences in study design, patient characteristics and lesion distribution can affect performance estimates.

Patients should therefore avoid choosing a test based solely on one sensitivity number.

Which Test Is Better at Detecting Precancerous Lesions?

This question is especially important because colorectal cancer screening is not only about finding cancer.

Some screening strategies can also identify precancerous lesions before they become cancer.

In the pivotal studies:

ColoSense: 41.3% sensitivity for advanced adenomas or serrated precancerous lesions in the primary combined category.

Cologuard Plus: 43.3% sensitivity for advanced precancerous lesions.

Again, the figures come from separate clinical studies and should not be interpreted as a direct head-to-head comparison.

The broader point is that both tests can detect some precancerous lesions, but neither detects every advanced precancerous lesion.

Which Test Has Fewer False Positives?

Specificity is one way to understand how often a test remains negative among people who do not have the target disease or lesion category.

ColoSense reported 85.6% specificity for its primary negative category.

Cologuard Plus reported 90.7% specificity for its primary negative category.

A higher specificity generally means fewer false-positive results in the relevant population.

However, the same caution applies:

These results come from separate studies and are not a randomized head-to-head comparison.

A person should not assume that choosing one test guarantees fewer false positives.

Does ColoSense Require Bowel Preparation?

No traditional colonoscopy bowel preparation is required for ColoSense.

The stool sample is collected at home and sent to a laboratory.

The FDA states that bowel preparation and dietary or medication restrictions are not necessary to complete the ColoSense test.

This is one of the main practical advantages of stool-based screening.

Does Cologuard Plus Require Bowel Preparation?

No traditional colonoscopy bowel preparation is required.

The test is designed for at-home stool collection.

This can make stool-based screening easier for people who are reluctant to undergo colonoscopy because of the bowel preparation and procedure.

However, if the stool test is positive, colonoscopy is still required.

That means avoiding bowel preparation at the screening stage does not necessarily mean avoiding it permanently.

How Often Do You Take ColoSense?

The American Cancer Society's 2026 colorectal cancer screening guideline lists multi-target stool RNA testing every three years as a preferred stool-based screening option.

ColoSense is therefore used as a periodic screening test rather than an annual stool test.

A person who receives a negative result should continue participating in a recommended colorectal cancer screening program.

How Often Do You Take Cologuard?

Cologuard Plus is also used every three years for appropriate average-risk screening.

This makes the testing interval similar to ColoSense.

The interval is different from:

• annual FIT;

• colonoscopy every 10 years for many average-risk adults with a normal examination;

• and CT colonography every five years.

The best interval depends on the test being used and the individual's risk profile.

Is ColoSense FDA Approved?

Yes.

The FDA approved ColoSense on May 3, 2024.

The FDA indication covers adults age 45 and older who are at average risk for colorectal cancer.

The FDA has also issued subsequent supplements to the ColoSense approval, including a September 2026 labeling-related supplement that extended the sample preservative shelf life from 12 months to 18 months.

FDA approval means the test has undergone regulatory review for its authorized use.

It does not mean the test is appropriate for every person or every type of colorectal cancer evaluation.

Is Cologuard Plus FDA Approved?

Yes.

Cologuard Plus has its own FDA premarket approval.

It is indicated for screening adults age 45 and older who are at average risk for colorectal cancer.

The FDA states that a positive result may indicate colorectal cancer or advanced precancerous lesions and should be followed by colonoscopy.

Does Medicare Cover ColoSense in 2026?

Yes, under Medicare's updated colorectal cancer screening policy and applicable eligibility requirements.

CMS added non-invasive biomarker tests to its colorectal cancer screening coverage framework effective June 8, 2026, subject to specific criteria.

CMS's claims-processing guidance specifically lists ColoSense under CPT code 0421U as a covered colorectal cancer screening service for dates of service on or after June 8, 2026.

Medicare's national coverage rules for non-invasive biomarker screening tests generally require that the beneficiary:

• be 45 through 85;

• be asymptomatic;

• be at average risk;

• receive an appropriate clinician order;

• and use an FDA-authorized test meeting CMS performance and other requirements.

The covered frequency is generally once every three years.

Does Medicare Cover Cologuard Plus?

Yes, Medicare covers eligible multi-target stool DNA screening tests under its colorectal cancer screening benefit.

CMS has listed Cologuard Plus as a covered colorectal cancer screening service.

For eligible beneficiaries, the standard multi-target stool DNA screening benefit is generally available every three years.

As with ColoSense, Medicare coverage depends on meeting the applicable eligibility requirements.

Is ColoSense Free With Medicare?

For an eligible Medicare beneficiary receiving a covered screening test under Medicare's preventive colorectal cancer screening benefit, beneficiary cost-sharing can be zero when the applicable Medicare requirements are met.

Patients should verify coverage before testing, particularly if they use Medicare Advantage or have circumstances that place them outside average-risk screening.

The fact that Medicare covers a test does not mean every related colorectal procedure is automatically free.

A positive stool test can lead to colonoscopy, which has its own Medicare coverage rules.

Is Cologuard Free With Medicare?

Eligible Medicare beneficiaries generally pay nothing for a covered multi-target stool DNA screening test when the applicable Medicare requirements are met and the provider accepts assignment.

The follow-up pathway is also important.

Medicare's complete colorectal cancer screening policy provides coverage for a follow-up screening colonoscopy after a positive covered non-invasive stool-based screening test when the applicable requirements are met.

Cost-sharing can change if tissue or a polyp is removed during colonoscopy.

What Happens If ColoSense Is Positive?

A positive ColoSense result is not a diagnosis of colorectal cancer.

The FDA says a positive ColoSense result may indicate:

• colorectal cancer;

• advanced adenoma;

• or a serrated precancerous lesion.

The appropriate next step is colonoscopy.

During colonoscopy, the healthcare professional can directly examine the colon and may remove polyps or take tissue samples.

The colonoscopy determines what the positive stool test actually represents.

The same basic principle applies to Cologuard.

What Happens If Cologuard Is Positive?

A positive Cologuard or Cologuard Plus result should be followed by colonoscopy.

The positive stool result cannot tell you whether the underlying finding is:

• cancer;

• a precancerous lesion;

• another type of polyp;

• or no significant neoplastic finding.

Colonoscopy is needed to determine what is actually present.

Repeating the stool test is not a substitute for the recommended colonoscopy.

Can ColoSense Replace Colonoscopy?

No.

ColoSense is a screening test.

It is not a replacement for diagnostic colonoscopy.

It is also not intended to replace surveillance colonoscopy in people at high risk.

If a person has a positive ColoSense result, colonoscopy is required for further evaluation.

This distinction is fundamental:

Screening test ≠ diagnostic procedure.

Can Cologuard Replace Colonoscopy?

No.

Cologuard is also a screening test.

It can provide a noninvasive way to begin colorectal cancer screening, but it cannot directly examine the colon or remove a polyp.

If the result is positive, colonoscopy is required.

For people with certain high-risk conditions or a history of colorectal cancer or adenomas, Cologuard may not be the appropriate screening or surveillance strategy.

Who Should Not Use ColoSense?

ColoSense is intended for average-risk adults age 45 and older.

The FDA states that it should not be used for people who are at higher risk for colorectal cancer.

Examples include people with:

• a personal history of colorectal cancer;

• a history of adenomas or related cancers;

• certain conditions associated with higher colorectal cancer risk;

• relevant hereditary cancer syndromes;

• or a recent positive colorectal cancer screening test.

Symptoms also matter.

A person with symptoms that require diagnostic evaluation should not simply use an at-home screening test instead of seeking medical care.

Who Should Not Use Cologuard?

The standard Cologuard and Cologuard Plus indications are for average-risk screening.

The tests are not intended to replace diagnostic colonoscopy for people with symptoms or high-risk conditions.

People with a history of colorectal cancer, adenomas, inflammatory bowel disease or certain hereditary syndromes may need a different screening or surveillance strategy.

Family history can also change the appropriate screening approach.

If you are not average risk, ask your healthcare professional before choosing an at-home stool test.

ColoSense vs Cologuard for People With a Family History

Neither test should automatically be chosen simply because it is convenient.

A family history of colorectal cancer or advanced polyps can change screening recommendations.

People with significant family history may need colonoscopy at an earlier age or at a different interval.

Therefore:

Do not use a standard average-risk stool-test schedule as a substitute for individualized screening advice.

This is especially important for people with a first-degree relative who had colorectal cancer or an advanced adenoma.

ColoSense vs Cologuard for People Who Have Symptoms

Neither test should be used to delay evaluation of concerning symptoms.

Symptoms can include:

• rectal bleeding;

• unexplained iron-deficiency anemia;

• persistent changes in bowel habits;

• unexplained abdominal symptoms;

• or unexplained weight loss.

Screening tests are intended for people without signs or symptoms of colorectal disease.

If symptoms are present, a healthcare professional may recommend diagnostic evaluation, which can include colonoscopy.

Which Test Is Easier to Take?

Both tests are designed to be completed at home.

That gives them a major practical advantage over colonoscopy.

You do not need to schedule a procedure simply to collect the stool sample.

However, convenience is not the only consideration.

A screening test is useful only if the person:

1. completes it;

2. receives the result;

3. understands the result;

4. and completes colonoscopy if the result is positive.

Therefore, the easiest test is not necessarily the test with the best molecular performance.

It may be the test you are actually willing to complete and follow through on.

Which Test Is Better for Someone Who Wants to Avoid Colonoscopy?

Both ColoSense and Cologuard can be reasonable options for an appropriate average-risk adult who prefers a noninvasive screening approach.

But neither eliminates the possibility of colonoscopy.

The key difference is timing.

With colonoscopy as the initial test:

screening → colonoscopy

With a stool-based test:

screening → positive result → colonoscopy

Most people with a negative stool test can continue stool-based screening according to the recommended interval.

But a positive result requires the next step.

Does a Negative ColoSense Mean You Do Not Have Cancer?

No.

A negative screening test reduces the likelihood that the test has detected its target conditions, but it does not guarantee that colorectal cancer or advanced precancerous disease is absent.

The FDA specifically states that a negative ColoSense result does not guarantee absence of colorectal cancer or advanced adenoma.

That is why people with a negative result should continue participating in a recommended colorectal cancer screening program.

Does a Negative Cologuard Mean You Do Not Have Cancer?

No.

A negative Cologuard result does not guarantee that colorectal cancer or precancerous lesions are absent.

No screening test detects every cancer or precancerous lesion.

A negative result means the test did not identify the signals that would trigger a positive result.

Continued screening is still necessary.

ColoSense vs Cologuard: Which Has Better Evidence?

Both have FDA-reviewed evidence.

ColoSense's FDA approval was based on its pivotal clinical study and includes a required post-approval study designed to provide additional evidence on clinical performance.

The FDA reported that ColoSense's pivotal study had 27 colorectal cancer cases in the primary average-risk cohort and required additional post-approval data to provide greater certainty around performance.

The post-approval study is designed to add additional colorectal cancer cases and further evaluate sensitivity for colorectal cancer, advanced adenomas and serrated precancerous lesions.

Cologuard Plus was evaluated in the larger BLUE-C pivotal study, with 18,911 participants in the primary effectiveness population.

This difference in evidence base is relevant when interpreting published performance numbers.

More study participants do not automatically make a test "better," but the size and design of a clinical evidence base matter when evaluating confidence in performance estimates.

Is ColoSense Included in the American Cancer Society Guidelines?

Yes.

The American Cancer Society's 2026 colorectal cancer screening guideline added multi-target stool RNA testing every three years as a preferred stool-based screening option.

The ACS describes stool-based tests and visual examinations as preferred approaches for colorectal cancer screening.

The guideline emphasizes that any abnormal non-colonoscopy screening result should be followed by timely colonoscopy.

This is significant because ColoSense represents the first RNA-based stool test included in the ACS colorectal screening recommendations.

Is Cologuard Included in the American Cancer Society Guidelines?

Yes.

The ACS 2026 guideline includes multi-target stool DNA testing every three years among preferred stool-based screening options.

That category includes established tests such as Cologuard.

The guideline therefore does not frame colorectal cancer screening as a choice between only colonoscopy and one stool test.

Instead, it recognizes several recommended screening options.

ColoSense vs Cologuard: Which Is Better for Medicare Patients?

For an eligible Medicare beneficiary, both can be options under Medicare's colorectal cancer screening coverage rules.

The practical differences are therefore less about whether one is "covered" and more about:

• eligibility;

• test availability;

• clinician recommendation;

• personal preference;

• and what happens if the result is positive.

Medicare's 2026 policy is particularly important because it recognizes qualifying non-invasive biomarker screening tests such as ColoSense.

That makes the 2026 landscape different from earlier years.

Does ColoSense Cost More Than Cologuard?

The answer depends on the patient's insurance and the current commercial pricing arrangements.

There is no reliable single nationwide self-pay price that should be presented as the standard cost of either test.

For insured patients, the out-of-pocket cost depends on the plan and applicable preventive-screening rules.

For Medicare beneficiaries who meet the requirements for covered screening, the applicable preventive benefit can result in no beneficiary cost-sharing for the screening test.

Patients should verify coverage before ordering.

Which Test Should You Choose?

For an average-risk adult age 45 or older, the decision can be approached through several questions.

Choose a stool-based test if:

• you want an at-home screening option;

• you prefer to avoid an initial invasive procedure;

• you are willing to complete the test on schedule;

• and you understand that a positive result requires colonoscopy.

Colonoscopy may be preferable if:

• you want direct examination of the colon;

• you want the opportunity to remove many polyps during the same procedure;

• you have risk factors that make stool-based average-risk screening inappropriate;

• or your healthcare professional recommends colonoscopy based on your medical history.

The best screening test is not necessarily the test with the highest number in a clinical study.

It is the recommended test that fits your risk level and that you will actually complete.

ColoSense vs Cologuard: Performance Comparison

The following table summarizes the FDA pivotal-study results.

Important: These percentages come from separate FDA clinical studies and should not be interpreted as a direct head-to-head comparison.

ColoSense vs Cologuard: Advantages and Limitations

The central limitation is shared by both tests:

Neither test can replace colonoscopy when the screening result is positive.

ColoSense vs Cologuard vs Colonoscopy

The three approaches serve different roles.

This table illustrates why it is not appropriate to ask only which test is "most accurate."

The tests perform different functions in the screening pathway.

What Happens After a Positive Stool Test?

The pathway is straightforward:

Step 1: At-home stool collection

The patient completes the prescribed test.

Step 2: Laboratory analysis

The laboratory analyzes the relevant biological markers.

Step 3: Result

The test is reported as positive or negative.

Step 4: If negative

The patient continues colorectal cancer screening according to the recommended schedule.

Step 5: If positive

The patient should arrange a follow-up colonoscopy.

Step 6: Colonoscopy

The healthcare professional examines the colon and can remove many polyps or obtain tissue samples.

Step 7: Pathology

If tissue is removed, pathology helps determine what was found.

The stool test is therefore not the endpoint.

It is one part of a larger screening pathway.

Can You Take ColoSense After a Positive Cologuard?

Generally, a person should not use another stool screening test simply to confirm a positive result.

A positive non-colonoscopy screening result requires appropriate follow-up.

The ACS recommends timely colonoscopy after an abnormal non-colonoscopy screening test.

Using another stool test instead of completing colonoscopy can delay definitive evaluation.

If you receive a positive Cologuard result, discuss the recommended colonoscopy with your healthcare professional rather than switching to ColoSense as a confirmation test.

Can You Take Cologuard After a Positive ColoSense?

The same principle applies.

A second stool test should not be used as a substitute for the recommended follow-up colonoscopy.

A positive ColoSense result means further evaluation is needed.

The FDA specifically directs patients with positive ColoSense results to colonoscopy.

What If You Are Worried About a False Positive?

False-positive results are a known limitation of noninvasive screening tests.

A positive result does not automatically mean cancer.

It means the test detected signals that warrant additional evaluation.

The colonoscopy may find:

• colorectal cancer;

• a precancerous lesion;

• another polyp;

• or no significant neoplastic lesion.

The possibility of a false positive is therefore one of the tradeoffs of stool-based screening.

The benefit is that the test can be completed without an initial invasive procedure.

What If You Are Worried About a False Negative?

No screening test is perfect.

A negative result does not guarantee that cancer or a precancerous lesion is absent.

That is why screening must be repeated according to the recommended interval.

People should also tell their healthcare professional if they develop symptoms between screening tests.

A new symptom can require medical evaluation regardless of a previous negative stool-test result.

Which Is Better: ColoSense or Cologuard?

For most readers, the safest answer is:

Neither is universally better.

ColoSense is a newer RNA-based stool screening technology with FDA approval and inclusion in the ACS 2026 preferred stool-based screening options.

Cologuard Plus is an established DNA-based multi-target stool test with strong FDA clinical-study performance and broad use in colorectal cancer screening.

Their pivotal studies reported different performance results, but those studies were not direct head-to-head comparisons.

The choice should therefore consider:

• whether you are average risk;

• your age;

• symptoms;

• family history;

• previous polyps;

• availability;

• insurance coverage;

• and which test you are most likely to complete.

The Bottom Line

ColoSense and Cologuard Plus are both FDA-approved at-home stool-based colorectal cancer screening tests for appropriate average-risk adults age 45 and older.

Their biggest technical difference is the molecular technology:

ColoSense → RNA + hemoglobin

Cologuard Plus → DNA methylation + hemoglobin

In FDA pivotal studies, ColoSense reported 92.6% sensitivity for colorectal cancer, while Cologuard Plus reported 95.3%. For their respective precancerous-lesion categories, the reported sensitivities were 41.3% and 43.3%.

But those numbers should not be interpreted as proof that one test is universally better because the studies were conducted separately.

The American Cancer Society's 2026 colorectal cancer screening guideline recognizes both multi-target stool RNA and multi-target stool DNA testing as preferred stool-based screening options, each at a three-year interval.

Medicare also expanded its colorectal cancer screening coverage in 2026 to qualifying non-invasive biomarker tests, including ColoSense under the applicable coverage requirements.

The most important rule is the same for both:

Positive stool test → follow-up colonoscopy.

Neither ColoSense nor Cologuard can diagnose colorectal cancer by itself, and neither replaces diagnostic or surveillance colonoscopy when colonoscopy is medically indicated.

For an average-risk adult who wants an at-home screening option, the best test is generally the recommended test that the person can complete consistently and follow up appropriately if the result is positive.

Frequently Asked Questions

Is ColoSense better than Cologuard?

There is no definitive head-to-head evidence establishing one as universally better. Their FDA pivotal studies reported different performance results, but the studies were conducted separately.

Is ColoSense more accurate than Cologuard?

ColoSense reported 92.6% colorectal cancer sensitivity in its pivotal study. Cologuard Plus reported 95.3%. Because the studies were separate, these numbers should not be treated as a direct comparison.

Is ColoSense an RNA test?

Yes. ColoSense is a multi-target stool RNA test that also detects occult hemoglobin.

Is Cologuard a DNA test?

Yes. Cologuard Plus is a multi-target stool DNA test that analyzes DNA methylation markers and hemoglobin.

How often do you take ColoSense?

The ACS 2026 guideline lists multi-target stool RNA testing every three years.

How often do you take Cologuard?

Cologuard Plus is used every three years for appropriate average-risk screening.

Does ColoSense require bowel preparation?

No traditional colonoscopy bowel preparation is required.

Does Cologuard require bowel preparation?

No traditional colonoscopy bowel preparation is required for the stool test.

What happens if ColoSense is positive?

A positive ColoSense result should be followed by colonoscopy.

What happens if Cologuard is positive?

A positive Cologuard or Cologuard Plus result should be followed by colonoscopy.

Does Medicare cover ColoSense in 2026?

Yes, qualifying non-invasive biomarker screening tests are covered under Medicare's updated colorectal cancer screening policy when the applicable criteria are met.

Does Medicare cover Cologuard Plus?

Yes, eligible multi-target stool DNA screening is covered under Medicare's colorectal cancer screening benefit.

Can ColoSense replace colonoscopy?

No.

Can Cologuard replace colonoscopy?

No.

Can I take Cologuard after a positive ColoSense result?

A second stool test should not be used as a substitute for the recommended follow-up colonoscopy.

Can I take ColoSense after a positive Cologuard result?

A second stool test should not be used to replace the recommended follow-up colonoscopy.

Which colorectal cancer screening test is best?

There is no single best test for everyone. The appropriate choice depends on risk, age, medical history, screening preferences and the likelihood that the person will complete the recommended screening and follow-up.

Official Medical Sources

This article was fact-checked against:

• U.S. Food and Drug Administration (FDA)

• FDA Premarket Approval records for ColoSense

• FDA Summary of Safety and Effectiveness Data for ColoSense

• FDA Premarket Approval records for Cologuard Plus

• FDA Summary of Safety and Effectiveness Data for Cologuard Plus

• Centers for Medicare & Medicaid Services (CMS)

• Medicare National Coverage Determination 210.3

• CMS 2026 colorectal cancer screening claims-processing guidance

• American Cancer Society 2026 colorectal cancer screening guideline

Key points reviewed:

• ColoSense is FDA-approved for average-risk adults age 45 and older.

• ColoSense is a multi-target stool RNA and hemoglobin test.

• Cologuard Plus is a multi-target stool DNA and hemoglobin test.

• Both are intended for average-risk colorectal cancer screening.

• Both require colonoscopy after a positive result.

• ACS 2026 includes mt-sRNA and mt-sDNA as preferred stool-based screening options every three years.

• Medicare's 2026 policy covers qualifying non-invasive biomarker screening tests every three years under specified criteria.

• CMS specifically lists ColoSense as a covered colorectal cancer screening test effective June 8, 2026.

• FDA clinical-study performance figures for ColoSense and Cologuard Plus come from separate pivotal studies and should not be treated as a direct head-to-head comparison.

Last reviewed for source accuracy: October 2026.

Medical disclaimer: This article is for general educational purposes only and is not a substitute for professional medical advice, diagnosis or treatment. Colorectal cancer screening recommendations, FDA labeling and insurance coverage can change. Talk with a qualified healthcare professional about which screening strategy is appropriate for your individual risk and medical history.