CMS NCD 210.3 adds ColoSense (0421U) for colorectal screening

CMS issued Change Request 14581 on August 27, 2026, as Transmittal 13921. The same CR updates both the National Coverage Determinations Manual (Pub 100-03) and the Medicare Claims Processing Manual (Pub 100-04), chapter 18, section 60.

The subject line is NCD 210.3 Screening for Colorectal Cancer–Non-Invasive Biomarker Tests. Effective date is June 8, 2026 (date of service). Implementation date is January 4, 2027.

This is not Thursday's October 2026 SNF CB HCPCS update. That CR is the SNF consolidated billing file. This CR is colorectal screening coverage and claims edits under NCD 210.3.

What CR 14581 adds for 0421U

CMS says effective June 8, 2026, non-invasive biomarker screening tests are appropriate colorectal cancer screening tests based on the criteria in NCD 210.3.

The Claims Processing Manual names ColoSense as CPT 0421U. The printed long descriptor is: Oncology (colorectal) screening, quantitative real-time target and signal amplification of 8 RNA markers (GAPDH, SMAD4, ACY1, AREG, CDH1, KRAS, TNFRSF10B, EGLN2) and fecal hemoglobin, algorithm reported as a positive or negative for colorectal cancer risk.

For dates of service on or after June 8, 2026, contractors shall accept and pay 0421U as a covered colorectal screening test when NCD 210.3 criteria are met. Payment is under the Clinical Laboratory Fee Schedule. Deductible and coinsurance do not apply.

Frequency, age, and diagnosis

Non-invasive biomarker colorectal cancer screening tests are covered once every 3 years. The business requirements say at least 2 years and 11 full months (35 months total) must elapse from the date of the last screening.

Patient criteria in the NCD and Claims Processing Manual:

• Age 45 to 85 years
• Asymptomatic (no signs or symptoms of colorectal disease, including lower gastrointestinal pain, blood in stool, or a positive non-invasive biomarker colorectal cancer screening test)
• At average risk of developing colorectal cancer (no personal history of adenomatous polyps, colorectal cancer, or inflammatory bowel disease, including Crohn's Disease and ulcerative colitis; no family history of colorectal cancers or adenomatous polyps, familial adenomatous polyposis, or hereditary nonpolyposis colorectal cancer)
• Provided with information about test performance and the importance of a follow-on colonoscopy if the test is positive

The test must be ordered by the physician, physician assistant, nurse practitioner, or clinical nurse specialist who will use the results in the management of the patient.

Providers shall report at least one of these diagnosis codes on the claim:

• Z12.11 Encounter for screening for malignant neoplasm of colon, or
• Z12.12 Encounter for screening for malignant neoplasm of rectum

Shared biomarker list (not a product dump)

CMS lists these as covered non-invasive biomarker screening tests under the same NCD 210.3 rules. This page does not turn that into a brand roundup. The list is here so the shared frequency and diagnosis rules are clear:

Test performance for coverage must meet either Criteria 1 (sensitivity ≥ 90% and specificity ≥ 87%) or Criteria 2 (sensitivity ≥ 79% and specificity ≥ 90%) for colorectal cancer versus colonoscopy, based on FDA labeling. The test must also be FDA market authorized for colorectal cancer screening, meet the FDA post-approval study in the Safety and Effectiveness Data, and be processed in a CLIA-certified laboratory.

Follow-on colonoscopy after a positive stool-based test

For dates of service on or after January 1, 2023, frequency limitations for screening colonoscopy (HCPCS G0105 and G0121) do not apply when the screening colonoscopy follows a positive result from a non-invasive stool-based test. The stool-based codes in that rule include CPT 82270, 81528, 0464U, and 0421U, plus HCPCS G0328. The furnishing practitioner identifies that scenario with the KX modifier on the screening colonoscopy claim.

CMS notes that a follow-on screening colonoscopy after a non-invasive stool-based or blood-based biomarker test is part of a complete colorectal cancer screening with no beneficiary cost sharing, when billed under those rules.

What MACs will and will not reopen

Business requirement 14581.04.11 says contractors shall not search for claims containing HCPCS 0421U with dates of service on or after June 8, 2026. They may adjust claims that are brought to their attention.

If a claim needs the new coverage rule before or around the January 4, 2027 systems date, bring that claim to the MAC. Do not wait for a file sweep.

What this is not

It is not a CMS-HCC or V28 mapping change. NCD 210.3 is colorectal cancer screening coverage. It does not assign an HCC. If the question is risk adjustment, use the model year you are actually coding in ICD-10 to HCC.

It is not Wednesday's October 2026 CLFS/CLIA update. That CR is the lab fee schedule quarterly. 0421U payment under the CLFS here is the colorectal screening claim path in chapter 18, not the PLA quarterly table.

It is not Tuesday's October 2026 HCPCS file / G0685. That ZIP is the Level II alpha-numeric file.

It is not the January 2027 NCD ICD-10 coding revisions. Those CRs maintain ICD-10 edit lists across many NCDs. This CR rewrites NCD 210.3 itself for non-invasive biomarker tests and adds 0421U.

Look up the official long descriptor in the encoder or the code book. Confirm Z12.11 / Z12.12 on the claim before you release it.