CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Comprehensive Genomic Profiling for Selecting Targeted Cancer Therapies

Defines medical coverage criteria for comprehensive genomic profiling (CGP) tests (tissue and plasma/liquid biopsy) for selecting targeted cancer therapies for Medicare Advantage and Commercial products, including specific named assays, required laboratory qualifications, patient clinical conditions, and CPT coding/billing guidance.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyComprehensive Genomic Profiling for Selecting Targeted Cancer Therapies

Policy CodePolicy N/A

Change TypeClarified coding and Medicare alignment

Effective DateApr 1, 2021

Next Review Date

Key ActionPrior authorization is required for Medicare Advantage Plans for named tests and is obtained via the online tool for participating providers.

SourceLink

POLICY UPDATE CHANGES

Guardant360 CDx code (0242U) effective 4/1/2021; prior to that an Unlisted CPT code must be used.

Medicare Advantage coverage criteria align with CMS NGS national coverage when performed in CLIA-certified labs, ordered by treating physician, and FDA-approved companion diagnostic indications are met.

6Named tests addressed

1Guardant360 code noted

3Provider updates published

This policy defines medical coverage criteria for Comprehensive Genomic Profiling (CGP) tests (tissue and plasma/liquid biopsy) used to select targeted cancer therapies for Medicare Advantage and Commercial products. The stance is mixed: certain named assays and indications are covered when specified criteria are met, while many expanded panels without established clinical utility are not supported by the evidence. The payer is Blue Cross Blue Shield - Rhode Island and the policy effective date is 2021-04-01.

Policy metadata — key facts

Policy titleComprehensive Genomic Profiling for Selecting Targeted Cancer Therapies

PayerBlue Cross & Blue Shield (Medicare Advantage and Commercial Products)

Effective date04/01/2021

Last review date04/01/2021

Next review date

Scope summaryDefines medical coverage criteria for comprehensive genomic profiling (tissue and plasma/liquid biopsy) to select targeted cancer therapies, names specific assays, required CLIA lab status, patient clinical conditions, and CPT coding/billing guidance.

Coverage stanceMixed — specific named tests covered for Medicare Advantage when criteria met; broader expanded panels have insufficient evidence for many commercial product decisions.

Guardant360 CDx CPT code (highlighted)0242U — New code effective 2021-04-01 (for dates of service prior to 2021-04-01, an Unlisted CPT code must be used)

Medical-Necessity Criteria

Medicare Advantage — Somatic (Acquired) Cancer Testing (Named Tests)

Covered when ALL of the following are met:

ALL of the following

Test is performed in a CLIA-certified laboratory and ordered by a treating physician
Patient has recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer
Patient has decided to seek further cancer treatment (e.g., therapeutic chemotherapy)
Patient has not been previously tested with the same test using NGS for the same cancer genetic content
The NGS diagnostic laboratory test has FDA approval or clearance as a companion in vitro diagnostic and has an FDA-approved or -cleared indication for use in that patient's cancer
Results are provided to the treating physician on a report template that specifies treatment options

Covered named tests (Medicare Advantage): Codes include Oncomine Dx Target Test (0022U), FoundationOne CDx (0037U), MSK-IMPACT (0048U), Praxis Extended RAS Panel (O111U), myChoice CDx (0172U)

Prior authorization required for Medicare Advantage Plans for named tests

Medicare Advantage — Guardant360 CDx Specific Criteria (Somatic / Plasma)

Guardant360 CDx covered when ALL of the following are met (code 0242U effective 2021-04-01):

ALL of the following

Test performed in CLIA-certified laboratory and ordered by a treating physician
Patient has a recurrent, relapsed, refractory, metastatic, or advanced solid tumor that did not originate from the central nervous system
Patient has decided to seek further cancer treatment and is a candidate for further treatment with a therapy that is either FDA-approved for that patient's cancer or has an NCCN Category 1 or 2A recommendation
FDA-approved indication or NCCN recommendation is based upon information about the presence or absence of a genetic biomarker tested for in the Guardant360 assay

Guardant360 CDx — Indications in NSCLC (At diagnosis and With disease progression)

Covered plasma EGFR testing with ctDNA when analysis is limited to specified EGFR variants and clinical context is met:

At diagnosis - eligible histologies

Advanced adenocarcinoma of the lung
Advanced squamous cell non-small-cell lung cancer
Large cell carcinoma
Non-small-cell lung cancer not otherwise specified

At diagnosis - analytic scope: Analysis performed on ONLY somatic variants in EGFR exons 19 through 21 (exon 19 deletions, L858R, T790M) in plasma specimens to detect ctDNA; used to predict treatment response to EGFR tyrosine kinase inhibitor therapy (erlotinib, gefitinib, afatinib, dacomitinib, osimertinib)

Germline (Inherited) Breast/Ovarian Cancer Testing — CGP

Covered when ALL of the following are met:

ALL of the following

Patient has ovarian or breast cancer
Patient has risk factors for germline (inherited) breast or ovarian cancer
There is a clinical indication for germline testing for hereditary breast or ovarian cancer
Patient has not been previously tested with the same germline NGS test for the same germline genetic content
The test has FDA approval or clearance

MSK-IMPACT Specific Indications (0048U)

Covered for evaluation of tumor tissue in the following clinical circumstances when performed in a CLIA-certified high complexity laboratory and ordered by a treating physician:

NSCLC-specific indications

Previously diagnosed patients with advanced (stage IIIB or IV) NSCLC who have not responded to at least one systemic therapy or who have progressed following resection, and who are candidates for treatment at time of testing
Newly diagnosed patients with advanced (stage IIIB or IV) NSCLC not treatable by resection or radiation with curative intent and who are suitable candidates for therapy at time of testing
Previously diagnosed patients with advanced (stage IIIB or IV) NSCLC who have been resistant to at least one targeted therapy, are able to undergo tumor tissue biopsy, and are suitable candidates for additional treatment at time of testing

CRC-specific requirement: For metastatic colorectal cancer (CRC): patient is a candidate for intensive chemotherapy with an anti-EGFR biologic agent and has not had RAS/BRAF testing (except after initiation of anti-EGFR therapy with evidence of acquired resistance)

Coding

Covered CPT — Medicare Advantage (named tests)CPTCovered

0022U	Oncomine Dx Target Test: Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA analysis, 23 genes
0037U	FoundationOne CDx: Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes
0048U	MSK-IMPACT: Oncology (solid organ neoplasia), DNA, targeted sequencing of protein-coding exons of 468 cancer associated genes
O111U	Praxis Extended RAS Panel: targeted KRAS and NRAS gene analysis (colon cancer)
0172U	myChoice CDx: somatic mutation analysis of BRCA1/BRCA2 and homologous recombination deficiency pathways
0242U	Guardant360 CDx: targeted genomic sequence analysis panel, cell-free circulating DNA analysis of 55-74 genes (New Code Effective 4/1/2021; prior to 4/1/2021 an Unlisted CPT code must be used)

Unlisted CPT — When no CPT existsCPT

Unlisted CPT

Use appropriate Unlisted CPT code for services referenced without assigned CPT; authorization required to determine service rendered and coverage

Provider Actions & Billing Rules

Prior Authorization

Prior authorization required for Medicare Advantage

Prior authorization is required for Medicare Advantage Plans for the named tests. Participating providers obtain authorization via the online tool.

Affected codes: 0022U, 0037U, 0242U, 0048U, O111U, 0172U
Method: online tool for participating providers

Prior Authorization

Prior authorization recommended for commercial products

Prior authorization is recommended (but not required) for Commercial Products. Unlisted CPT codes require authorization to determine the service rendered and coverage.

Unlisted CPT
Recommendation: prior authorization recommended (not required) for commercial products

Billing Rule

Use of Unlisted CPT codes before 2021-04-01 for Guardant360 CDx

Guardant360 CDx was assigned CPT code 0242U effective 2021-04-01. For dates of service prior to 2021-04-01, file claims using an appropriate Unlisted CPT code.

Codes: 0242U, Unlisted CPT
Note: 0242U effective 2021-04-01; prior to that file with Unlisted CPT

Documentation Required

Report requirements

Results must be provided to the treating physician using a report template that specifies treatment options. FDA-approved/cleared companion diagnostic status and FDA indication must apply when reporting.

Requirement: provide results to the treating physician using a report template specifying treatment options
Requirement: FDA-approved/cleared companion diagnostic status and applicable FDA indication must apply

Denial Risk

Duplication exclusion

Claims may be denied if the patient was previously tested with the same test using NGS for the same genetic content.

Duplication exclusion: prior identical NGS testing for same genetic content may lead to claim denial

Background & Evidence

Comprehensive genomic profiling (CGP) evaluates multiple genetic markers at once to identify potential targeted cancer treatments. The policy distinguishes expanded panels—which test a wide variety of markers without demonstrated clinical utility—from FDA-cleared or -approved companion diagnostics that have specific, labeled indications and supporting evidence.

The document notes that broad molecular panels generally lack demonstrated clinical benefit as a group (for example, the SHIVA randomized trial showed no difference in progression-free survival compared with standard treatment), supporting caution about routine use of expanded panels.

When the policy’s specified criteria are met (e.g., testing performed in a CLIA-certified laboratory, ordered by the treating physician, and the NGS test is an FDA companion in vitro diagnostic with an FDA-approved indication for the patient’s cancer), Medicare Advantage coverage aligns with the CMS national coverage determination for Next Generation Sequencing (NGS) (NCD 90.2) and related local determinations.

Evidence	Summary
SHIVA randomized trial	Randomized trial (SHIVA) of expanded molecular profiling showed no difference in progression-free survival versus standard treatment; used as evidence that broad panels lack demonstrated clinical benefit overall.
FDA approvals noted	Multiple FDA clearances/approvals for named assays: FoundationOne CDx (2017), Oncomine Dx Target Test (2017), MSK-IMPACT (2017 de novo clearance), Guardant360 CDx (August 2020).

Alternative to Tissue Biopsy: Obtaining new tissue is not feasible (for example, insufficient tissue, no amenable lesion, or biopsy cannot be performed).

CLIA-certified laboratory: Laboratory certified under the Clinical Laboratory Improvement Amendments to perform high-complexity testing.

Coding/billing note: the Guardant360 CDx CPT code 0242U is effective 2021-04-01; for dates of service prior to 2021-04-01 an Unlisted CPT code must be used.

OpenPayer

Comprehensive Genomic Profiling for Selecting Targeted Cancer Therapies

Coverage Summary

Medical-Necessity Criteria

Coding

Provider Actions & Billing Rules

Background & Evidence

Medicare Determinations

Revision History

Name	Number	Type
Next Generation Sequencing (NGS)	90.2	NCD
Genomic Sequence Analysis in the Treatment of Solid Neoplasms	L37810	LCD