CurrentAloha CarePolicy MP-26

Genetic Testing Colon Cancer Treatment

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Coverage policy for genetic and molecular tests used to guide treatment decisions in individuals with diagnosed colorectal cancer, applicable to AlohaCare QUEST Integration (Medicaid) and Medicare plans.

Policy Summary

PayerAloha Care

PolicyGenetic Testing Colon Cancer Treatment

Policy CodePolicy MP-26

Change TypeNo material changes

Effective DateDec 13, 2019

Last ReviewDec 1, 2020

Next Review DateDec 1, 2020

Key ActionObtain prior authorization and document medical necessity; testing covered only when results will change clinical management.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

KRAS/NRAS/BRAFlisted as medically necessary when criteria met

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CurrentAloha CarePolicy MP-26

Genetic Testing Colon Cancer Treatment

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Policy Summary

PayerAloha Care

PolicyGenetic Testing Colon Cancer Treatment

Policy CodePolicy MP-26

Change TypeNo material changes

Effective DateDec 13, 2019

Last ReviewDec 1, 2020

Next Review DateDec 1, 2020

Key ActionObtain prior authorization and document medical necessity; testing covered only when results will change clinical management.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

KRAS/NRAS/BRAFlisted as medically necessary when criteria met

required for genetic testing

CLIA & CAPlaboratory certification required

Experimental listmultiple named tests considered experimental/investigational

Refs: 7number of reference items listed

Multiple codesprocedure and PLA codes referenced

Coverage Criteria for Genetic and Molecular Testing

KRAS/NRAS/BRAF mutation testing

Covered when ALL of the following are met:

KRAS/NRAS/BRAF testing criteria: 1. The patient has a diagnosis of colorectal cancer; AND 2. Treatment with anti-EGFR monoclonal antibodies (e.g., cetuximab and/or panitumumab) is being considered; AND 3. Testing will be performed on tumor tissue (metastatic or recurrent CRC tissue, or primary CRC tumor tissue); AND 4. The specific test is either (a) FDA-approved to determine treatment eligibility, OR (b) a laboratory-developed test (LDT) with completed validation demonstrating analytical validity and clinical validity for determining treatment eligibility.

MSI and/or MMR IHC testing

Covered when ALL of the following are met:

MSI/MMR testing criteria: 1. The patient has a diagnosis of colorectal cancer; AND 2. Testing will be performed on tumor tissue (metastatic or recurrent CRC tissue, or primary CRC tumor tissue); AND 3. The specific test is performed in a CLIA and CAP-certified laboratory AND is either (a) FDA cleared or approved, OR (b) an LDT with completed validation demonstrating analytical validity and clinical validity.

Multigene companion diagnostic testing

Covered when the following is met:

Multigene tests are medically necessary when the test is an FDA-approved companion diagnostic for a potential treatment regimen (example: Praxis Extended RAS Panel [KRAS and NRAS mutations]).

Genetic testing of genes beyond those specified in this policy for guiding colorectal cancer (CRC) treatment, and testing performed on specimen types other than CRC tumor tissue, are not supported by evidence and are explicitly classified as experimental and investigational. The policy further requires that requests for repeat testing include documentation of medical necessity (for example, recurrence of disease or a change in disease behavior).

The policy identifies multiple commercial and proprietary assays as Experimental & Investigational due to insufficient peer‑reviewed evidence of clinical utility in CRC. Examples referenced in the policy text and coding table include assays such as the SEPT9 promoter methylation analysis (CPT 81327) and urine metabolite panels (CPT 0002U), which the document lists among tests considered experimental for colorectal oncology.

Testing of additional genes not listed in the covered indications, and any genetic testing for CRC treatment performed on non‑tumor specimen types, is considered not medically necessary and classified as experimental/investigational. The policy requires that valid CRC tumor tissue be used for somatic testing when results are intended to guide anti‑EGFR or other targeted therapies.

Several named assays and panels are explicitly listed as considered experimental and investigational because of limited published evidence demonstrating clinical utility in CRC. The list in the policy includes, but is not limited to, tests such as MatePair (CPT 0013U), miR‑31now (CPT 0069U), MSK‑IMPACT (CPT 0048U), OncoTarget/OncoTreat (CPT 0019U), and PolypDX (CPT 0002U).

Covered Indications

Patients diagnosed with colorectal cancer when anti-EGFR therapy is being considered (for KRAS/NRAS/BRAF testing) or when MSI/MMR testing on tumor tissue is needed.

Covered indications for testing:

Covered indication: Patients diagnosed with colorectal cancer when anti-EGFR therapy is being considered (for KRAS/NRAS/BRAF testing) or when MSI/MMR testing on tumor tissue is needed.

Tests related to colorectal/colon oncology including detection of somatic mutations (e.g., NRAS), promoter methylation (SEPT9), gene expression profiling, tumor sequencing including MSI assessment, microRNA expression profiling, and other molecular assays.

Covered indications — tests and assay types related to colorectal oncology include:

Tests related to colorectal/colon oncology: Detection of somatic mutations (e.g., NRAS), promoter methylation assays (e.g., SEPT9), mRNA gene expression profiling (e.g., 12-gene recurrence score), tumor sequencing panels including assays that assess microsatellite instability, microRNA expression profiling (e.g., miR-31-3p), and other molecular assays described (examples include whole genome/whole transcriptome sequencing and large targeted tumor panels such as a 468-gene panel).

Not Covered / Experimental Tests

The policy specifically enumerates a set of tests that are considered not covered for CRC treatment because they lack demonstrated clinical utility. Tests named include COLARIS, ColonSentry, ColoNext, Colopath, ColonSeq, ColoSeq, Colovantage (CPT 81327), MatePair (CPT 0013U), miR‑31now (CPT 0069U), MSK‑IMPACT (CPT 0048U), OmniSeq RNA‑Sequencing, Onco4D (CPT 0083U), OncoTarget/OncoTreat (CPT 0019U), OncotypeDx Colon, and PolypDX (CPT 0002U).

The policy reiterates that certain assays are labeled Experimental & Investigational — for example, the quantitative assessment of three urine metabolites used to estimate likelihood of adenomatous polyps (CPT 0002U) is identified in the document as experimental for colorectal oncology. Such assays are not considered medically necessary for guiding CRC treatment.

Provider Actions, Documentation & Authorization

Prior Authorization

Prior authorization required for genetic testing

Prior authorization is required for genetic testing; testing is covered only when test results will change clinical management and lead to improved health outcomes.

Prior Authorization

Prior authorization required

Prior authorization is required; tests are covered only when results will change clinical management and lead to improved health outcomes.

Billing Rule

Coding and Procedure Codes

Relevant CPT/HCPCS codes (informational)mixed

81210	BRAF gene analysis, V600 variant(s).
81275	KRAS gene analysis; variants in exon 2 (eg, codons 12 and 13).
81276	KRAS gene analysis; additional variant(s) (eg, codon 61, codon 146).
81301	Microsatellite instability analysis of markers for mismatch repair deficiency, includes comparison of neoplastic and normal tissue, if performed.
81311	NRAS gene analysis, variants in exon 2 and exon 3 (eg, codons 12, 13, 61).
81327	SEPT9 promoter methylation analysis (Oncology - colon).
81525	Oncology (colon), mRNA, gene expression profiling by real-time RT-PCR of 12 genes, algorithm reported as a recurrence score.
0002U	Oncology (colorectal), quantitative assessment of three urine metabolites by LC-MS/MS, algorithm reported as likelihood of adenomatous polyps.
0013U	Oncology (solid organ neoplasia), gene rearrangement detection by whole genome NGS, DNA, fresh or frozen tissue or cells.
0019U	Oncology, RNA, gene expression by whole transcriptome sequencing, predictive algorithm reported as potential targets for therapeutic agents.

1–10 of 11

1/2

Listed CPT/PLA codes and descriptionsmixed

81311	NRAS gene analysis, variants in exon 2 (eg, codons 12 and 13) and exon 3 (eg, codon 61)
81327	SEPT9 (Septin9) promoter methylation analysis (eg, colorectal cancer)
81525	Oncology (colon), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (7 content and 5 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a recurrence score
0002U	Oncology (colorectal), quantitative assessment of three urine metabolites (ascorbic acid, succinic acid and carnitine) by LC-MS/MS, algorithm reported as likelihood of adenomatous polyps
0013U	Oncology (solid organ neoplasia), gene rearrangement detection by whole genome next-generation sequencing, DNA, fresh or frozen tissue or cells, report of specific gene rearrangement(s)
0019U	Oncology, RNA, gene expression by whole transcriptome sequencing, formalin-fixed paraffin-embedded tissue or fresh frozen tissue, predictive algorithm reported as potential targets for therapeutic agents
0048U	Oncology (solid organ neoplasia), DNA, targeted sequencing of protein-coding exons of 468 cancer-associated genes, including interrogation for somatic mutations and microsatellite instability, matched with normal specimens
0069U	Oncology (colorectal), microRNA, RT-PCR expression profiling of miR-31-3p, formalin-fixed paraffin-embedded tissue, algorithm reported as an expression score
0083U	Oncology, response to chemotherapy drugs using motility contrast tomography, fresh or frozen tissue, reported as likelihood of sensitivity or resistance to drugs or drug combinations

Definitions

inv-19: LDT — Laboratory Developed Test

DefinitionLaboratory Developed Test (LDT): Any test developed by a laboratory without FDA approval or clearance.

Acceptable for coverage when validatedAn LDT is acceptable for determining treatment eligibility only when it has completed validation demonstrating analytical and clinical validity (per coverage criteria).

Regulatory contextLDTs are distinct from FDA-cleared/approved tests and are specifically referenced in the policy's laboratory and test-type requirements.

inv-20: Lynch Syndrome associated

ScopeLynch Syndrome associated (HNPCC-Related Cancer) includes colorectal, endometrial, gastric, biliary tract, brain, small bowel, ureter, pancreas, ovarian, renal pelvis, and sebaceous gland adenomas/keratocanthomas.

Clinical relevance

Background

Colorectal cancer treatment decisions depend on tumor biology; testing for tumor somatic alterations directs use of targeted therapies. In particular, KRAS/NRAS/BRAF mutations predict lack of benefit from anti‑EGFR monoclonal antibodies and should be assessed on tumor tissue when anti‑EGFR therapy is being considered. The policy requires testing to be performed in laboratories with CLIA and CAP certification and accepts FDA‑approved tests or laboratory‑developed tests with completed validation demonstrating analytical and clinical validity.

Policy Revision History

2019-12-13policy_created

Policy MP-26 created and became effective.

2020-12-01policy_retiredLatest

Policy MP-26 retired (document indicates retirement on this date).

Policy Summary

PayerAloha Care

PolicyGenetic Testing Colon Cancer Treatment

Policy CodePolicy MP-26

Change TypeNo material changes

Effective DateDec 13, 2019

Last ReviewDec 1, 2020

Next Review DateDec 1, 2020

Key ActionObtain prior authorization and document medical necessity; testing covered only when results will change clinical management.

SourceLink

On This Page

Listed CPT/PLA procedure codes (use for billing/documentation)

The policy enumerates specific CPT and PLA procedure codes for the listed genetic and molecular tests that should be used for billing and identification of tests.

Examples include CPT/PLA codes: 81311, 81327, 81525, 0002U, 0013U, 0019U, 0048U, 0069U, 0083U.

Step Therapy

Exclude anti‑EGFR therapy for RAS/BRAF‑mutant patients

Exclude anti‑EGFR therapy (cetuximab, panitumumab) for patients with RAS (exon 2, 3, or 4 of KRAS or NRAS) or BRAF mutations; FDA labeling indicates these drugs are not recommended for patients with RAS mutations or when RAS status is unknown.

Documentation Required

Repeat testing requires medical‑necessity documentation

Requests for repeat testing must include documentation of medical necessity, such as disease recurrence or change in disease behavior.

Documentation must state the medical necessity reason (e.g., recurrence, change in disease behavior).

Billing Rule

Billing: use listed procedure/PLA codes

Use the policy’s listed procedure and PLA codes when submitting claims or documenting tests; codes in the policy include (but are not limited to) 81311, 81327, 81525, 0002U, 0013U, 0019U, 0048U, 0069U, and 0083U.

Note

No explicit authorization/denial triggers defined

The policy text does not specify explicit authorization or denial triggers beyond the requirement that prior authorization is required and testing be medically necessary to change management.

No explicit automatic authorization or denial criteria (triggers) are stated in the cited policy text.

Note

Provider action: follow listed codes, prior‑auth, and documentation rules

(Reserved) Provider actions in this section reference the policy’s listed tests and codes; follow prior‑authorization and documentation requirements outlined elsewhere in the policy when ordering or billing these assays.

Identification of Lynch-associated cancers can guide genetic evaluation and management for hereditary colorectal cancer syndromes.

TerminologyReferred to in the policy as 'Lynch Syndrome associated' (aka HNPCC-Related Cancer).

inv-21: MSI — Microsatellite Instability (MSI)

DefinitionMicrosatellite Instability (MSI): the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR) genes.

MSI-H meaningMSI-H is evidence that MMR is functioning abnormally and is indicative of certain hereditary colorectal cancers.

Use in policyMSI testing (or MMR IHC) on tumor tissue is specified as a covered test when performed in CLIA- and CAP-certified labs and when FDA-cleared/approved or validated as an LDT.

inv-22: NRAS — NRAS gene analysis

Gene and variantsNRAS gene analysis: variants in exon 2 (codons 12 and 13) and exon 3 (codon 61) are relevant for colorectal carcinoma.

CPT code exampleCPT 81311 corresponds to NRAS gene analysis for variants in exon 2 and exon 3 (eg, codons 12, 13, 61).

Clinical implicationNRAS variants are considered in somatic tumor testing to guide colorectal cancer treatment decisions (eg, anti-EGFR therapy selection).

inv-23: SEPT9 — SEPT9 (Septin9) promoter methylation

Test targetSEPT9 (Septin9) promoter methylation analysis used in colorectal cancer detection.

CPT code exampleCPT 81327 corresponds to SEPT9 promoter methylation analysis (oncology - colon).

ApplicationSEPT9 promoter methylation is listed among molecular assays related to colorectal/colon oncology in the policy's coding section.