Where this LCD applies
Each contract number is a jurisdiction on the remittance; the policy binds claims processed under these contracts and no others.
Billing and coding: diagnoses and procedure codes
Since 2019 the codes live in the companion article rather than the LCD. Billing and Coding A60310 (Billing and Coding: MolDX: Non-Next Generation Sequencing Targeted Molecular Panel Tests for Targeted Therapy in Cancer) carries the diagnosis and procedure lists the contractor loads as the claims edit. CPT codes are shown as bare numbers because the descriptors are licensed by the AMA; HCPCS Level II descriptors are public and shown.
A60310: Billing and Coding: MolDX: Non-Next Generation Sequencing Targeted Molecular Panel Tests for Targeted Therapy in Cancer (Billing and Coding)
- Covered ICD-10-CM codes
- 680
- 1 group
- Non-covered ICD-10-CM codes
- 0
- Procedure codes listed
- 1
- Full article
- cms.gov record
| ICD-10-CM | Description (FY2027) |
|---|---|
| C00.0 | — |
| C00.1 | — |
| C00.2 | — |
| C00.3 | — |
| C00.4 | — |
| C00.5 | — |
| C00.6 | — |
| C00.8 | — |
| C00.9 | — |
| C01 | Malignant neoplasm of base of tongue |
| C02.0 | — |
| C02.1 | — |
| C02.2 | — |
| C02.3 | — |
| C02.4 | — |
| C02.8 | — |
| C02.9 | — |
| C03.0 | — |
| C03.1 | — |
| C03.9 | — |
| C04.0 | — |
| C04.1 | — |
| C04.8 | — |
| C04.9 | — |
Procedure codes: 81479.
Coverage indications, limitations and medical necessity
This policy describes and clarifies coverage for molecular panel tests for Non -Next Generation Sequencing Targeted Molecular Panel Tests for Targeted Therapy in Cancer. The determination outlines the medical necessity, indications, limitations, and required documentation for biomarker testing to ensure appropriate patient selection and effective utilization.
Criteria for Coverage
Non -Next Generation Sequencing Targeted Molecular Panel Tests for Targeted Therapy in Cancer are covered when ALL of the following are met:
• The patient has a diagnosis of cancer for which molecular testing of the tumor will inform treatment AND has not been previously tested by a molecular panel test for the same cancer indication for the same genetic content. NOTE: A negative result (no clinically actionable mutations found) by the non-NGS test may be followed by an NGS test that includes additional necessary genes and genomic positions and/or other predictive testing information.
• Testing recommended by national consensus guidelines for the purpose of informing medical management decisions can be achieved by a non-NGS method AND one of the following is true:
• Testing by next-generation sequencing (NGS) is not feasible ( i.e., adequate specimen for appropriate NGS testing is not available); OR
• The panel (i) provides a rapid result with superior (to NGS) turnaround times less than the ASCO-recommended 10 business days from sample receipt in the laboratory, allowing for the prompt and timely management of the patient AND (ii) identifies known, common, and necessary predictive and actionable biomarkers with an accuracy for measured analytes comparable to NGS testing, such that NGS testing can safely be precluded.
• The test accurately detects the most common genes and genomic positions required for the identification of clinically relevant FDA-approved therapies with a companion diagnostic biomarker for the given cancer type.
• The test has been validated in the intended-use population and with the intended-use sample types.
• The test has satisfactorily completed a Technical Assessment (TA) by the Molecular Diagnostic Services Program (MolDX ® ) to ensure analytical validity (AV), clinical validity (CV) and clinical utility (CU) standards are met.
• Clinical validity (CV) of any analytes or profiles must be established through a study published in the peer-reviewed literature for the intended use of the test in the intended population with demonstrated reproducibility across clinical study cohorts. If the test relies on an algorithm, the algorithm must be validated in a cohort that is not a development cohort for the algorithm.
• Tests utilizing a similar methodology or evaluating a similar analyte(s) to a test for which existing coverage has been established must demonstrate equivalent or superior test performance (i.e., sensitivity and/or specificity) when used for the same indication in the same intended use population.
Notes:
• Reference to specific tests in this LCD does not automatically imply coverage.
• NGS-based panel tests must fulfill criteria outlined in LCDs L38158, MolDX: Next-Generation Sequencing for Solid Tumors and L38176, MolDX: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and Suspected Myeloid Malignancies.
• Non-NGS-based tests for the diagnosis of BCR-ABL-negative myeloproliferative neoplasms must fulfill criteria outlined in LCD L40022, MolDX: Non-Next Generation Sequencing Tests for the Diagnosis of BCR-ABL Negative Myeloproliferative Neoplasms.
Summary of evidence (opening)
The Importance of Molecularly - Informed Targeted Therapies in Cancer
Molecular testing of tumors has become a standard of care for many cancer types, and an increasing number of molecularly targeted therapies (therapies that exploit discrete targets in the genome) have become available in recent years. For example, approximately 70% of tumors from patients with metastatic lung adenocarcinoma have an actionable driver mutation 1-4 and at least 1 FDA - approved therapy currently exists that targets the following non-small cell lung cancer (NSCLC) oncogenic drivers: Anaplastic lymphoma kinase (ALK), B-Raf proto-oncogene (BRAF), Epidermal Growth Factor Receptor (EGFR), human epidermal growth factor receptor 2 (HER2), Kirsten rat sarcoma (KRAS) G12C variant, mesenchymal-epithelial transition exon 14 (METex14), neurotrophic tyrosine receptor kinase (NTRK) rearranged during transfection (RET), and ROS proto-oncogene 1 (ROS1). 5,6
Molecularly targeted therapies have resulted in improved patient management and outcomes for various cancer types. 7-10 For patients with advanced non-squamous NSCLC, a number of studies have found that the availability of genomic results prior to the initiation of treatment is associated with a statistically significant improvement in overall survival (OS). 11-16 Studies have also shown improved time to therapy discontinuation, the avoidance of ineffective therapies (such as immune checkpoint inhibitors (ICPIs) among ALK/EGFR/RET/ROS1-positive patients), and improved progression free survival (PFS) when first-line therapy is initiated on the basis of molecular findings. 14-18 Importantly, when actionable oncogenic driver (AOD) status is unknown and driver-positive patients first receive chemo-ICPIs, patients face the risk of severe immune-related events on subsequent targeted therapy. 18,19 A multisite retrospective observational analysis found that advanced NSCLC patients harboring AODs who were empirically treated with non-tyrosine kinase inhibitor (non-TKI) therapy while awaiting genomic test results had significantly inferior outcomes than those initially treated on the basis of genomic results. 16 Notably, patients who were not treated until molecular results were available fared better despite having begun treatment approximately 25 days later (range: 6-55 days for NGS-tissue test result availability). 16 A large retrospective analysis of a nationwide electronic health record–derived database of patients with advanced NSCLC and an AOD found that those who switched to a targeted therapy within 42-84 days after a biomarker test result had similar outcomes to those who received targeted treatment as a first-line therapy. 6 Notably, patients with AODs who never received targeted treatment had worse OS and PFS than all cohorts. 6
In patients with advanced colorectal cancer (CRC), first-line treatment includes the use of targeted therapies informed by AODs, some of the most common being in the BRAF, KRAS, and NRAS genes, in addition to microsatellite instability (MSI)/mismatch repair (MMR) status. 20,21 Importantly, the integration of such targeted agents into combination regimens has improved treatment efficacy and survival outcomes. 20,22 In a study of 3,216 patients with an array of advanced cancers including NSCLC, CRC, and breast cancer, patients who received molecularly-informed targeted therapies had better survival outcomes compared with chemotherapy only (hazard ratio [HR], 0.66, [95% CI, 0.52 to 0.84], P 10
The contractor cites 84 sources in the bibliography; the full summary and analysis of evidence are in the CMS record.
Dates, lineage and related policies
- Original determination effective
- 2026-10-12
- Current revision effective
- 2026-10-12
- Last reviewed by the contractor
- 2026-07-20
- MCD version
- 6
Other related documents: A60530 (Response to Comments).
Using this policy on a claim
Match the documented indication to the covered indications above before the service is scheduled, carry a diagnosis from the article's covered list on the claim line, and keep the elements the documentation section asks for in the record, because the contractor can request it later through medical review. A denial under this policy arrives as CARC 50 with remark N115; the LCD lookup guide walks through the appeal path and the Advance Beneficiary Notice rules, and the Wisconsin Physicians Service Insurance Corporation hub lists every other active policy from the same contractor.
The same policy title at other contractors
Contractors often adopt each other's policies and then revise them separately, so the criteria and the diagnosis lists drift apart. The topic comparison lines up every version.
Frequently asked questions
What does LCD L40278 cover?
• Testing recommended by national consensus guidelines for the purpose of informing medical management decisions can be achieved by a non-NGS method AND one of the following is true: The full indications and limitations are reproduced on this page from the CMS Medicare Coverage Database export of September 24, 2026.
Which states does LCD L40278 apply to?
Wisconsin Physicians Service Insurance Corporation applies it to Medicare claims in AK, AL, AR, AZ, CA, CO, CT, DE, FL, GA, HI, IA, ID, IL, IN, KS, KY, LA, MA, MD, ME, MI, MO, MS, MT, NC, ND, NE, NH, NJ, NM, NV, OH, OK, OR, PA, RI, SC, SD, TN, TX, UT, VA, VT, WA, WI, WV, WY. A Local Coverage Determination binds only the contractor that wrote it; the same service in another jurisdiction is judged under that contractor's own policy or, where none exists, claim by claim.
Which diagnosis codes support medical necessity under LCD L40278?
The companion billing and coding article A60310 lists 680 ICD-10-CM codes in 1 group that support medical necessity; the first 24 appear on this page and the complete list is in the article on cms.gov.
How do I appeal a denial under LCD L40278?
The remittance carries claim adjustment reason code 50 with remark code N115, naming the LCD. Compare the documented indication with the policy's covered indications and the article's diagnosis list, then file a redetermination within 120 days with the record attached; if the service genuinely falls outside the policy, the patient can be billed only when a valid Advance Beneficiary Notice was obtained before the service.
Sources
Every figure on this page is taken from the CMS publications below, as released by the Centers for Medicare & Medicaid Services. Projection built 2026-10-02. Verify against the primary file before billing or contracting decisions.
- Medicare Coverage Database, current LCD exportVersion MCD release 2026-09-24 · effective 2026-09-20 · file lcd.csvSHA-256 2fcc4251b6ddd1eb…
- Medicare Coverage Database, current Billing and Coding Articles exportVersion MCD release 2026-09-24 · effective 2026-09-20 · file article.csvSHA-256 f31932f1df3b4035…
- ICD-10-CM FY2027 code descriptionsVersion FY2027 · effective 2026-10-01 · file icd10cm_codes_2027.txtSHA-256 3c0583a38ee0e848…
Disclaimer
The policy text and code lists are reproduced from the CMS Medicare Coverage Database export as an operational reference. Verify against the current LCD and article on cms.gov before billing; coverage depends on the full record and the contractor. Not legal, clinical or billing advice.