CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

InVisionFirst (plasma-based ctDNA comprehensive genomic profiling) for advanced non‑small cell lung cancer (NSCLC)

Policy governs medical necessity and prior authorization for the InVisionFirst plasma-based comprehensive genomic profiling test (ctDNA NGS) for patients with advanced (Stage IIIB/IV) non-small cell lung cancer (NSCLC) when tissue-based CGP is infeasible or at progression, affecting Medicare Advantage and Commercial members of BCBSRI.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyInVisionFirst (plasma-based ctDNA CGP) for advanced NSCLC

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization (required for Medicare Advantage; recommended for Commercial) and document that tissue-based CGP is infeasible (QNS) or biopsy is contraindicated when requesting InVisionFirst.

SourceLink

Stage IIIB/IVindicated disease stage

36–37genes in assay

33%sufficient tissue (validation)

67%insufficient tissue (validation)

19%serious AE rate (biopsy)

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Coverage and Medical Necessity Criteria

Medical Necessity Criteria

Covered when ALL of the following are met:

Population: Patient has advanced (Stage IIIB/IV) non-small cell lung cancer (NSCLC)

Timing/Indication: (A) At diagnosis when results for EGFR (SNVs/indels), ALK and ROS1 rearrangements, and BRAF (SNVs) are not available AND tissue-based comprehensive genomic profiling (CGP) is infeasible (quantity not sufficient [QNS]) or invasive biopsy is medically contraindicated; OR (B) At progression for patients progressing on EGFR tyrosine kinase inhibitors (TKIs); OR (C) At progression for patients progressing on or after chemotherapy or immunotherapy who have not been tested for EGFR/ALK/ROS1/BRAF and tissue-based CGP is infeasible

Test: Requested test is InVisionFirst (plasma-based circulating tumor DNA next-generation sequencing)

Some self-funded groups may have contractual exclusions under the state Biomarker Testing Mandate (RI.GL §27-19-81). When a group has excluded biomarker-related services, specific genetic testing services (including certain expanded or proprietary assays) may be designated as covered only with authorization, not medically necessary, or not covered. Refer to the member's Benefit Booklet and the related Genetic Testing Services and Proprietary Laboratory Analyses policies for the applicable list of covered, excluded, or authorization-required services.

Coverage and benefits for genetic and genomic testing can vary by contract and by group. Prior to ordering, confirm coverage in the member's Evidence of Coverage, Benefit Booklet, or Subscriber Agreement. Tests that do not meet the medical necessity criteria in this policy, or that are expressly excluded by the member's contract, are not covered.

Genomic Target	FDA‑Approved Targeted Therapy / Regimen	Notes
EGFR
Osimertinib; other EGFR TKIs (eg, erlotinib, gefitinib, afatinib)
Identifies EGFR SNVs and indels that predict response to oral EGFR inhibitors

Billing and Coding

Covered CPT CodesCPTCovered

0388U	Oncology (non-small cell lung cancer), next-generation sequencing with identification of single nucleotide variants, copy number variants, insertions and deletions, and structural variants in 37 cancer related genes, plasma, with report for alteration detection (New Code Effective 7/1/2023)
81479	Unlisted molecular pathology procedure (used for dates of service to 07/01/2023)

Tissue tumor fraction note

Tissue tumor fraction limitEvaluating somatic mutations in formalin-fixed, paraffin-embedded (FFPE) tissue below 5% allele frequency is challenging due to analytical variables in tissue preservation and processing

Contributing factorsAnalytical variables include tissue fixation/processing, specimen volume, and tumor cell fraction within the specimen

Clinical implicationLow allele fraction in FFPE may lead to incomplete or failed tissue-based comprehensive genomic profiling (CGP)

Authorization, Documentation, and Laboratory Interaction

Prior Authorization

Prior Authorization Required

Prior authorization is required for Medicare Advantage Plans and recommended for Commercial Products. The ordering physician must obtain any required prior authorization; laboratories and laboratory representatives are not permitted to obtain authorization, participate in the authorization process, or act on behalf of the ordering physician.

Prior authorization required for Medicare Advantage Plans; recommended for Commercial Products
Only the ordering physician may be involved in authorization, appeals, or other administrative processes
Laboratories, laboratory representatives, or third parties may not obtain authorization on behalf of the ordering physician

Note

Provider action: Ensure the ordering physician completes and submits any prior authorization requests and supporting clinical documentation. Do not rely on laboratories or third parties to initiate or complete authorization workflows.

Ordering physician must lead authorization, appeals, and documentation submission

Key Terms and Test Description

InVisionFirst (plasma ctDNA NGS)

Test nameInVision — plasma-based circulating tumor DNA (ctDNA) next-generation sequencing (NGS) assay for detection of genomic alterations in NSCLC

Intended useDetects clinically relevant genomic alterations to identify targets linked to FDA-approved therapies at diagnosis or progression

Gene contentAssay targets 36 commonly mutated genes (InVision clinical validation described 36 genes)

Insufficient tissue (QNS) definition

Definition (QNS)Quantity not sufficient (QNS) — insufficient tissue specimen for tissue-based comprehensive genomic profiling (CGP)

When usedQNS is an accepted justification to perform plasma-based ctDNA testing (InVision) when tissue-based CGP is infeasible

Permitted Lines of Therapy

first-line

Line: Use at diagnosis when guideline-recommended tissue results are not available and tissue-based comprehensive genomic profiling (CGP) is infeasible (QNS) or biopsy/invasive procedure is medically contraindicated

second-line

Line: Use at progression for: (1) patients progressing on EGFR TKIs; OR (2) patients progressing on or after chemotherapy or immunotherapy who lack prior testing for EGFR/ALK/ROS1/BRAF and tissue-based CGP is infeasible

Biomarkers and Assay Scope

EGFR — biomarker requirement

BiomarkerEGFR (epidermal growth factor receptor) single nucleotide variants (SNVs) and insertions/deletions (indels)

When requiredTesting indicated when EGFR results are not available at diagnosis or at progression on EGFR tyrosine kinase inhibitors (TKIs)

Clinical relevanceEGFR mutations predict response to EGFR inhibitors (eg, erlotinib, gefitinib, osimertinib, afatinib) and comprise up to ~15% of NSCLC in the US

ALK — biomarker requirement

BiomarkerALK rearrangements (fusions)

When requiredTesting indicated when ALK rearrangement results are not available at diagnosis or when guiding targeted therapy

Clinical Background and Rationale

Many patients with non-small cell lung cancer (NSCLC) present with advanced, incurable disease (Stage IIIB/IV). Identification of targetable oncogenic driver alterations such as EGFR, ALK, ROS1, BRAF, MET, and ERBB2 can directly inform targeted therapy selection. Standard tissue-based comprehensive genomic profiling (CGP) is the preferred approach but can be limited by insufficient tissue (QNS), procedural risk from repeat biopsy, and gaps in testing. Plasma-based circulating tumor DNA (ctDNA) next-generation sequencing assays (eg, InVisionFirst) provide a noninvasive alternative to detect actionable genomic alterations when tissue-based CGP is infeasible or at disease progression, facilitating targeted treatment decisions.

Policy Revision History

2023-11publicationLatest

Policy published/updated in Provider Update (July/November 2023) reflecting coverage and coding for InVisionFirst, including CPT 0388U effective 2023-07-01 and use of 81479 for dates of service prior to 2023-07-01.

2023-07-01coding update

New CPT code 0388U became effective for InVisionFirst (plasma NGS for NSCLC); previously CPT 81479 was used for dates of service before this date.

notice

Prior authorization requirement and laboratory authorization restrictions reiterated for Medicare Advantage and recommended for Commercial Products.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyInVisionFirst (plasma-based ctDNA CGP) for advanced NSCLC

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Do not delegate authorization tasks to laboratories or their representatives

Documentation Required

Required Documentation

Document the clinical rationale for testing, including involvement of the ordering physician and evidence that tissue-based comprehensive genomic profiling (CGP) is infeasible (for example, quantity not sufficient [QNS] or medically contraindicated invasive procedures). Include copies of prior pathology reports, imaging, and any notes supporting insufficient tissue or clinical contraindication to further biopsy.

Evidence of QNS or medical contraindication for tissue-based CGP (e.g., pathology report, clinician note)
Clinical history and indication for InvisionFirst or other liquid CGP testing
Order signed or authenticated by the ordering physician

Denial Risk

Authorization and Laboratory Involvement

Services performed without required prior authorization will be denied as the laboratory's financial liability and may not be billed to the member. If a laboratory or third party participates in obtaining authorization on behalf of the ordering physician, BCBSRI will treat that as a policy violation and may impose penalties including termination from the provider network.

Unauthorized laboratory services will be denied and billed to the laboratory, not the member
Participation by laboratories or third parties in authorization constitutes a policy violation and may result in sanctions

Supporting evidenceValidation studies found many specimens do not yield complete results and only ~33% had sufficient tissue for complete CGP, underscoring use of plasma testing when QNS

Clinical relevanceALK rearrangements occur in ~4% of NSCLC patients and predict response to ALK-targeted inhibitors (eg, crizotinib, ceritinib, alectinib)

ROS1 — biomarker requirement

BiomarkerROS1 rearrangements (fusions)

When requiredTesting indicated when ROS1 results are not available at diagnosis or when tissue-based CGP is infeasible

Clinical relevanceROS1 fusions are guideline-recommended targets though testing rates have historically been low in community practice

BRAF — biomarker requirement

BiomarkerBRAF single nucleotide variants (SNVs)

When requiredTesting indicated when BRAF SNV results are not available at diagnosis or at progression

Clinical relevanceBRAF V600E mutations have approved targeted therapy (eg, dabrafenib plus trametinib) for metastatic NSCLC