Currentblue cross blue shield - kansasPolicy N/A

Proteomic Testing for Systemic Therapy in Non-Small-Cell Lung Cancer

This policy governs the use of serum proteomic tests (including the VeriStrat assay) to predict survival or guide systemic therapy selection in patients with non-small-cell lung cancer for members of Blue Cross and Blue Shield of Kansas.

Policy Summary

Payerblue cross blue shield - kansas

PolicyProteomic Testing for Systemic Therapy in Non-Small-Cell Lung Cancer

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateApr 16, 2021

Next Review DateJan 13, 2026

Key ActionVerify member benefits and obtain prior authorization or benefit verification when required, noting the policy considers proteomic testing experimental/investigational and not supported for coverage.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

VeriStratnamed proteomic test discussed

Experimentalpolicy stance

HRs <1OS/PFS association direction

81538CPT code listed

CLIAregulatory status

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Coverage Determination

Not covered (experimental/investigational)

Policy stance: The use of proteomic testing, including but not limited to the VeriStrat assay, is considered experimental/investigational for all uses in the management of non-small-cell lung cancer.

No clinical use is supported by this policy.

Experimental / Investigational

Not covered

Experimental/Investigational Stance: Use of proteomic testing (including VeriStrat) for any use in the management of non-small-cell lung cancer is considered experimental/investigational.

Policy statement applies to all intended uses and patient populations in NSCLC.

Clinical validity evidence

Evidence summary (study-level prognostic associations)

General: Multiple prospective and retrospective studies evaluated VeriStrat classification (Good vs Poor) in advanced NSCLC across different treatments; many studies report better overall survival (OS) and progression-free survival (PFS) for VeriStrat 'good' compared with 'poor', with hazard ratios frequently <1 though effect sizes vary by cohort and treatment.

See study tables and cohort summaries in the evidence review (eg, Taguchi et al., Grossi et al., Spigel et al.).

Evidence requirement node

Evidence summary informing coverage considerations

Evidence requirements for coverage: Coverage for proteomic testing to guide systemic therapy in NSCLC should be supported by prospective studies demonstrating clinical utility (improved health outcomes) in the specific intended-use population and treatment context; the reviewed literature lacks prospective evidence for first-line use and for guiding therapy in early-stage (I/II) post-surgical or medically inoperable stage I/II disease.

Derived from lack of identified studies and limitations in study design and applicability.

Evidence-based coverage considerations

Evidence summary regarding use of VeriStrat to predict therapy response in NSCLC:

Prognostic association: Randomized trials and retrospective analyses consistently report VeriStrat 'good' versus 'poor' is prognostic for OS and PFS in advanced NSCLC cohorts (examples include PROSE, TOPICAL, BR.21 subset, MARQUEE, LUX-Lung 8 analyses).

Prognostic associations reported across multiple study types.

Predictive value for differential treatment benefit: Evidence for predictive value (differential benefit between EGFR TKI and chemotherapy) is mixed: PROSE suggested a differential benefit in the second-line setting favoring chemotherapy for VeriStrat 'poor', but other trials (eg, EMPHASIS, TOPICAL) and retrospective analyses did not consistently demonstrate a predictive interaction or were limited by design or applicability.

See PROSE (positive interaction) and subsequent trials with inconsistent findings.

Limitations and applicability: Many trials enrolled patients and used treatment strategies not consistent with current guideline-based sequencing (eg, EGFR TKIs in EGFR wild-type/unknown patients), had incomplete EGFR mutation data, lacked contemporary comparator arms (eg, modern chemotherapy or immunotherapy), or had early termination/limited enrollment, reducing applicability to current practice.

Evidence synthesis

Summary of evidence-based conclusions

Clinical validity and utility summary: Studies show VeriStrat classification (good vs poor) is associated with survival outcomes in multiple retrospective studies and in randomized trials, but evidence is limited by heterogeneity, outdated treatment regimens, small samples, lack of independence from EGFR-variant status, and absence of direct evidence that management guided by the test improves patient health outcomes.

No direct RCT evidence demonstrates improved outcomes from test-guided management; analytic identification of constituent proteins remained incomplete in several reports.

The policy states that the use of serum proteomic testing, including the commercially described VeriStrat assay, is considered experimental / investigational for all uses in the management of non-small-cell lung cancer (NSCLC). This classification excludes proteomic testing from coverage for any intended clinical use in NSCLC because the evidence does not establish clinical utility.

Proteomic assays (including VeriStrat) are explicitly excluded from coverage for all uses in NSCLC as experimental/investigational; the policy makes no supported clinical indications for proteomic testing to predict survival or to guide selection of systemic therapy in NSCLC.

The provided excerpts do not define detailed patient-selection or exclusion criteria tied to coverage decisions. Study cohorts often excluded small cell histology and in some analyses excluded or separately reported squamous versus nonsquamous histology, but the policy text does not provide explicit clinical eligibility rules for proteomic testing.

No published studies were identified that used VeriStrat to inform therapeutic decision-making for patients with stage I or II NSCLC after surgical resection; the evidence review explicitly notes the absence of studies applying the proteomic test in this post-surgical early-stage population.

The policy indicates there are no identified studies using VeriStrat to inform therapy for patients with stage I or II NSCLC who are medically inoperable or post-surgery; consequently, no evidentiary support exists for those early-stage clinical scenarios.

The review found no published studies that assessed use of VeriStrat to inform treatment selection or imaging surveillance for newly diagnosed stage I or II NSCLC; the evidence base for these indications is absent in the cited literature.

Inclusion of CPT/HCPCS codes in the policy is informational only. The policy cautions that code listing does not constitute coverage; listed codes are medically necessary only if performed according to the Policy section and applicable member contract.

Based on the evidence review, proteomic testing (including VeriStrat) is not established as medically necessary for prediction of survival or for selection of systemic therapy in NSCLC because clinical utility (improved patient health outcomes when management is guided by the test) has not been demonstrated.

The rationale for the policy conclusion is that although VeriStrat classification (good vs poor) is associated with overall and progression-free survival in multiple retrospective cohorts and some randomized-trial sample analyses, there is no direct evidence that using the test to guide therapy selection improves patient outcomes; clinical validity is limited by heterogeneous populations, outdated treatment contexts, and lack of independence from EGFR-variant status.

While the document describes that proteomic testing is considered experimental/investigational, the provided fragments do not contain explicit phrasing that uses the label 'not medically necessary' in every chunk; the policy instead conveys exclusion via the experimental/investigational determination.

The evidence does not support using VeriStrat to predict response to first-line targeted therapies or first-line chemotherapy in newly diagnosed advanced NSCLC. Randomized trials and cohort analyses either did not use VeriStrat to direct first-line therapy or enrolled populations and used treatment strategies that are not consistent with current guideline-based sequencing.

Using VeriStrat to direct EGFR tyrosine kinase inhibitor (TKI) therapy in EGFR wild-type or unselected populations is not aligned with contemporary guidelines; NCCN and trial evidence indicate EGFR TKIs should be used based on confirmed sensitizing EGFR variants, and several trials that evaluated VeriStrat did not reflect current molecular-testing–driven treatment pathways.

A central evidence gap is that no trials were identified demonstrating that management strategies guided by VeriStrat improve health outcomes. The available data are primarily prognostic associations and do not provide direct evidence of clinical utility for therapy selection.

The policy reiterates that procedure and diagnosis codes shown are for informational purposes only; the presence of a code in the coding section does not automatically indicate coverage—codes are considered medically necessary only when the service meets the policy's clinical criteria and member contract.

Indications Studied / Considered

Prognostic assessment in advanced NSCLC

Intended use population: Prognostic assessment of patients with advanced (stage IIIB/IV or recurrent) NSCLC being considered for systemic therapy (chemotherapy, EGFR TKI, or combination regimens).

Studies included chemotherapy-naive and previously treated patients; many cohorts were predominantly non-squamous histology.

Prognostic classification evidence

Association with outcomes: Multiple retrospective and prospective cohorts report hazard ratios comparing VeriStrat 'good' versus 'poor' for OS and PFS, often favoring 'good' (HRs <1), though estimates vary across studies and cohorts.

Examples include Wu et al., Yang et al., and other validation analyses reporting significant HRs for OS and PFS.

Not Covered / Exclusions

Proteomic testing, including VeriStrat, is specifically listed in the 'Not covered' section as not covered for prediction of survival or selection of systemic therapy in NSCLC, reflecting the experimental/investigational policy stance.

The policy reiterates that proteomic assays (including VeriStrat) are excluded from coverage for any use to predict survival or guide systemic therapy selection in NSCLC because clinical utility has not been demonstrated.

Although the policy states proteomic testing is not covered, the provided excerpts do not enumerate specific, granular test-use exclusions tied to particular clinical scenarios beyond the broad experimental/investigational classification.

The policy highlights the lack of evidence supporting use of VeriStrat to select therapy in stage I/II post‑surgery or medically inoperable stage I/II NSCLC, and therefore these indications are not supported for coverage.

Use of VeriStrat to select first-line targeted therapies or first-line chemotherapy in newly diagnosed advanced NSCLC is not supported by identified studies and is therefore not covered under the evidence presented.

The policy identifies a key evidence limitation: there is no direct evidence that management guided by VeriStrat improves health outcomes, which underpins the 'not covered' determination.

The coding section reiterates a cautionary note that listing a code does not guarantee coverage. No explicit test-specific code-based exclusions are provided in the excerpt.

Procedure and Billing Codes

Listed CPT/HCPCS CodesCPT

81235	EGFR gene analysis, common variants (e.g., exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q)
81538	Oncology (lung), mass spectrometric 8-protein signature, including amyloid A; serum prognostic/predictive algorithm reported as good versus poor overall survival

Note

Coding and coverage caveat

The inclusion or exclusion of the codes listed in this section is for informational purposes only and does not imply that services described by these codes are a covered benefit or will be reimbursed. Coverage and payment depend on the member's contract and whether the service meets the medical necessity criteria in this policy.

Billing Rule

Coding and prior authorization note

CPT codes 81235 and 81538 are listed in this policy. These codes are considered medically necessary only when performed in accordance with the medical necessity criteria and other requirements described in this policy. Prior authorization or documentation requirements may apply per the payer's policies and the member's benefit plan.

Affected codes: 81235, 81538

Provider Steps and Documentation Requirements

Prior Authorization

Prior authorization and benefit verification — verify benefits and authorize where required

Proteomic testing (including VeriStrat) is categorized as experimental/investigational and not supported for coverage; providers should verify member benefits and obtain prior authorization where required by the member’s contract, recognizing the policy does not support coverage.

Verify member benefits with BCBSKS Customer Service
Obtain prior authorization when required by the member contract, but note policy stance

Prior Authorization

Prior authorization not applicable — experimental/investigational tests not covered

Proteomic testing (e.g., VeriStrat) is classified as experimental/investigational and is not a covered service; prior authorization cannot be used to render these tests covered for NSCLC management.

Tests are considered experimental/investigational for all NSCLC uses
Prior authorization will not make an excluded test covered

Definitions and Test Descriptions

Proteome / Proteomics — definition

DefinitionProteome/proteomics — the complete complement of proteins produced by an organism or cellular system; proteomics is the large-scale study of these proteins, which may be measured by mass spectrometry or protein microarray from tumor or bodily fluids.

Clinical relevanceA cancer cell's proteome is related to its genome and may vary by cell type and over time; proteomic signatures have been investigated as biomarkers in cancer, including NSCLC.

Measurement methodsProteomic signatures for cancer have been measured using mass spectrometry platforms (eg, MALDI‑MS) or protein microarrays.

VeriStrat assay — description

Assay typeVeriStrat assay — a commercially available serum‑based proteomic test using matrix‑assisted laser desorption ionization mass spectrometry (MALDI‑MS).

Result categories

Clinical Background

The policy background notes that NSCLC comprises the majority of lung cancers and that prognosis depends on stage; advanced disease has poor 5-year survival, providing clinical context for why prognostic markers have been investigated but underscoring the need for outcome-improving management strategies.

Eligibility Criteria

No eligibility requirement top-level nodes are specified in the provided policy excerpt.

Policy Revision Timeline

2015-10-01policy_posted

Policy originally posted (original effective date).

2021-04-16effective_date

Current effective date set for this policy.

2026-01-13last_reviewLatest

Policy most recently reviewed; clinical evidence and coding sections updated as needed during review.

Policy Summary

Payerblue cross blue shield - kansas

PolicyProteomic Testing for Systemic Therapy in Non-Small-Cell Lung Cancer

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateApr 16, 2021

Next Review DateJan 13, 2026

SourceLink

On This Page

Described in study relevance and limitation summaries.

Assessment of prognosis in advanced NSCLC cohorts

Assessment of prognosis in advanced NSCLC cohorts — investigational/prognostic biomarker findings

Study types and findings: Randomized controlled trials (eg, PROSE, EMPHASIS, TOPICAL) and retrospective analyses of RCTs (eg, BR.21 subset, LUX-Lung 8, MARQUEE) have evaluated VeriStrat as a prognostic and/or predictive biomarker; many analyses show VeriStrat status is associated with survival but were limited in predictive consistency and applicability to contemporary treatment pathways.

Retrospective subsets often lacked comparator arms representative of current standard care.

Lack of direct outcome improvement evidence

Clinical utility gap: There is no direct evidence that using VeriStrat to guide therapy selection improves patient outcomes; prognostic association alone is insufficient to recommend test-directed changes in therapy.

Preferred evidence would be RCTs comparing management with and without the test; such direct evidence is not available for contemporary treatment pathways.

Use of mass spectrometric 8-protein signature (VeriStrat-type) studied and listed in coding/references

Assay and coding: A mass spectrometric serum proteomic 8-protein signature (eg, VeriStrat-type, MALDI‑MS) has been evaluated in multiple studies and is referenced in coding (CPT 81538) and in the published literature cited in this review.

Analytic identity of all constituent proteins/features remained under investigation in several studies; see coding section for CPT 81538.

Documentation Required

Coding documentation

Use CPT 81538 to report the mass spectrometric 8-protein lung oncology signature. Use CPT 81235 to report EGFR common variant analysis.

Prior Authorization

Prior authorization not specified — follow member contract processes

The provided excerpts do not specify explicit prior authorization requirements for proteomic testing; providers should follow member contract and plan-specific prior authorization processes.

No explicit prior authorization rules stated in the policy excerpts

Prior Authorization

Prior authorization likely required — unsupported indications likely denied

Proteomic testing to predict response for first‑line therapies or to guide treatment in early‑stage (I/II) post‑surgical patients is unsupported by identified studies; requests for such uses are likely to require prior authorization and are likely to be denied absent evidence of investigational approval.

No studies identified using VeriStrat to guide first‑line therapy or early‑stage post‑surgical treatment
Such indications lack evidentiary support and are likely to be denied

Prior Authorization

Prior authorization considerations — PROSE evaluated second‑line contexts, not first‑line

Evidence does not show VeriStrat has been used to direct first‑line therapy in newly diagnosed advanced NSCLC; the PROSE RCT evaluated VeriStrat in a second‑line context (erlotinib vs chemotherapy), limiting applicability to first‑line decisions.

PROSE trial evaluated VeriStrat in second‑line erlotinib vs chemotherapy
No direct evidence supporting first‑line use to direct therapy selection

Note

Established genomic testing preferred — use guideline-directed molecular testing

Guideline-directed molecular testing for established genomic alterations (eg, sensitizing EGFR variants) guides targeted TKI use; proteomic testing is not a substitute and is not recommended by this policy for directing targeted therapy.

NCCN recommends EGFR‑variant testing to guide EGFR TKI selection
Proteomic assays are not endorsed as an alternative to established genomic testing

Note

Reference to standard management — follow guideline-based care

Standard guideline-based systemic therapy is the comparator practice; the policy indicates proteomic testing has not been established to change standard management pathways.

Standard medical management remains the comparator
Proteomic testing is not established to alter guideline-based therapy selection

Step Therapy

No step therapy rules specified — policy does not define sequencing

No step therapy rules are provided in the policy excerpts; the document reviews clinical studies and coding but does not specify step therapy sequencing or authorization requirements.

Policy does not define step therapy rules in provided excerpts

Note

Adherence to current treatment sequencing — studies used outdated regimens

Many evaluated studies used treatment regimens (eg, EGFR TKIs in EGFR‑unknown or wild‑type populations, or EGFR+VEGF combinations) that are no longer consistent with current guideline-recommended sequencing; providers should adhere to current standards when considering treatment sequencing.

Studies used outdated treatment contexts (EGFR TKI in EGFR‑unknown/wild‑type)
Apply current guideline-recommended sequencing rather than proteomic classification

Note

Relevance to current step therapy — trial populations differ from current practice

Trials often used erlotinib in populations not consistent with current guideline-recommended sequencing (eg, EGFR wild‑type patients), limiting the relevance of those trials to contemporary step therapy pathways.

TOPICAL and PROSE included erlotinib use in unselected/EGFR‑unknown populations
Applicability to current sequencing is limited

Step Therapy

Provider actions not applicable — no step therapy sequencing defined

This policy focuses on evidence review and coding; it does not define step therapy sequencing requirements or impose specific step edits based on proteomic classification.

Policy does not establish step therapy rules; follow plan-specific utilization management if present

Documentation Required

Benefit verification — verify benefits and legal mandates

Verify member benefits and consider state/federal mandates and the member’s contract language before determining eligibility for coverage of proteomic testing.

Contact BCBSKS Customer Service to verify benefits
Consider plan and state/federal mandates first

Documentation Required

Required test context documentation — record assay type, timing, and intended use

When submitting proteomic test results or requests, document that the assay is a serum proteomic test performed prior to treatment or at progression and clearly state the intended use (prediction of OS/PFS or to influence selection of systemic therapy).

Document test type (serum proteomic assay), timing (pre‑treatment or at progression), and intended use (prognosis or treatment selection)

Documentation Required

Specimen and clinical data reporting — record sample type, histology, performance status

Document specimen type and pertinent clinical data that were used for testing—studies typically used pretreatment frozen serum or baseline plasma samples and reported tumor histology and ECOG performance status where available.

Record specimen (pretreatment frozen serum or baseline plasma)
Include histology and performance status in documentation

Documentation Required

Required clinical outcome documentation — record OS/PFS and adjustment variables

When proteomic test results are used in clinical decision‑making, include documentation of relevant clinical outcomes (OS, PFS) and adjustment variables considered (age, sex, histology, performance status) as reported in evidence summaries.

Document OS and PFS outcomes and any adjustments for age, sex, histology, or ECOG PS

Documentation Required

Supporting trial documentation — include trial cohort details when relevant

Clinical trial reports included sample sizes, histology, ECOG performance status distribution, and EGFR‑variant status where available; include these supporting trial data when relevant to test interpretation.

Include trial/sample sizes, histology, ECOG PS, and EGFR‑variant status if available

Documentation Required

Medical necessity and member contract — codes only medically necessary per Policy and contract

Procedures and codes listed in the coding section are medically necessary ONLY if performed according to the Policy section; refer to the member contract at the time of service to determine coverage eligibility.

Codes medically necessary only if consistent with Policy criteria
Confirm member contract benefits at time of service

Denial Risk

Provider actions summary — proteomic testing considered experimental/investigational

Use of proteomic testing (including VeriStrat) for any use in the management of non‑small‑cell lung cancer is considered experimental/investigational and not supported for coverage; providers should not expect coverage unless policy and member contract criteria are met.

Proteomic testing (including VeriStrat) is experimental/investigational for all NSCLC uses
Tests are not supported for coverage under this policy

Denial Risk

Denial for experimental/investigational tests — likely denial basis

Requests for proteomic testing for NSCLC are likely to be denied on the basis that these tests are experimental/investigational and not medically necessary according to this policy.

Denial reason: experimental/investigational exclusion for all uses in NSCLC

Prior Authorization

No explicit prior authorization/denial triggers — follow standard processes

The policy does not identify specific prior authorization or documentation triggers that would automatically permit coverage; absence of explicit triggers in the excerpts means usual benefit verification and prior authorization processes apply.

No explicit prior authorization or denial triggers stated in provided text

Denial Risk

Lack of evidence for first‑line use — no supporting studies

No studies identified use of VeriStrat to guide first‑line targeted therapy or first‑line chemotherapy in newly diagnosed advanced NSCLC; lack of direct evidence for first‑line use may lead to denial for such intended use.

No studies supporting use to guide first‑line therapy
Requests for first‑line guidance likely unsupported

Denial Risk

Limits of evidence for early-stage NSCLC — no supporting studies for stage I–II uses

No studies were identified that used VeriStrat to inform therapeutic options for stage I–II NSCLC after surgery or in medically inoperable stage I–II disease; such uses are unsupported by the evidence reviewed and may be denied.

No evidence for stage I–II post‑surgical or medically inoperable stage I–II uses

Billing Rule

Coding and coverage caveat — code listing not coverage (repeat)

Inclusion of CPT or other codes in the policy’s coding section does not constitute member coverage; listed codes are medically necessary only if the procedure is performed according to the Policy section and member contract.

Code listing is informational; verify policy clinical criteria and member contract for coverage

Billing Rule

Coding inclusion note — listing does not imply coverage (repeat)

Inclusion or exclusion of codes in the document does not imply coverage or reimbursement; the presence of a code does not change the policy’s experimental/investigational stance.

Code inclusion does not alter coverage determination

Note

Ordering clinician unspecified — no explicit ordering requirements

The excerpts do not specify who may order the test; while oncology specialists commonly order proteomic testing in studies, the policy provides no explicit ordering‑clinician requirements.

No explicit ordering-provider restrictions in policy excerpts
Oncology specialists commonly involved in study settings

Note

Ordering clinician context — oncology specialists commonly involved

No specific ordering-provider requirements are provided in the policy excerpt; tests in the literature were commonly ordered by treating medical oncologists in trial and clinical contexts.

Ordering by treating medical oncologists is typical in studies
Policy contains no formal ordering restrictions

Note

Ordering context — tests performed in oncology trial settings

Studies were typically performed in oncology trial settings and tests were ordered in that context; the policy does not prescribe which specialties may order the test.

Tests ordered in oncology trial settings
Policy does not restrict ordering specialties

Note

Ordering-provider study notes — policy does not specify specialties

Physician decision‑making studies report tests were ordered for NSCLC, but the policy does not specify which specialties may order the test; no explicit ordering‑provider requirements are provided in this excerpt.

Physician decision‑making studies included various ordering clinicians
No ordering restrictions in policy excerpt

Note

Ordering provider absence — follow plan procedures

No specific ordering‑provider requirements are provided in this policy excerpt; providers should follow their plan’s ordering and authorization procedures.

Follow plan‑specific ordering and prior authorization rules

Classifies patients as 'Good' or 'Poor' based on an 8‑peak/protein signature (reported in literature as an 8‑protein or 8‑peak signature).

Commercial detailsMarketed through a single laboratory; vendor describes 'Good' as more likely to respond to standard treatment and 'Poor' as associated with aggressive disease and potential alternative strategies.

Proteomic testing (VeriStrat) — classification and intended use

Classification outputVeriStrat proteomic testing classifies NSCLC patients into 'Good' or 'Poor' prognostic groups based on MALDI‑MS derived proteomic features (8‑peak signature).

Intended clinical useIntended to predict expected survival outcomes (OS/PFS) with standard systemic therapies and to potentially inform selection between EGFR TKIs and other treatments in patients with wild‑type or unknown EGFR status.

Test limitations notedThe test reports a proteomic signature rather than gene variants; clinical utility to guide therapy selection has not been established in prospective studies.

Clinical purpose — prognostic and potential predictive use

Primary clinical purposePredict expected survival outcomes (overall survival and progression‑free survival) for patients with NSCLC receiving systemic therapies.

Potential predictive roleMay be evaluated for differential response to EGFR tyrosine kinase inhibitors versus chemotherapy, particularly in EGFR wild‑type or unknown populations, but evidence is mixed and limited.

Evidence gapNo direct evidence demonstrates that using VeriStrat to guide therapy selection improves patient health outcomes; prospective utility is lacking.

VS (VeriStrat) — 'Good' / 'Poor' classification

Reported classification labelsVeriStrat (VS) classification reported as 'Good' or 'Poor' based on serum/plasma proteomic profile.

Biological correlatesSome components of the 8‑peak signature include fragments of serum amyloid A protein 1; specific protein identities and their specificity for malignancy are not fully determined.

Use in studiesVS classification has been used in multiple retrospective and prospective cohorts to stratify OS and PFS outcomes.

OS / PFS / TTP — endpoint definitions

Overall survival (OS)OS — time from treatment or randomization to death from any cause; primary outcome used in studies assessing VeriStrat prognostic associations.

Progression‑free survival (PFS)PFS — time from treatment or randomization to disease progression or death; commonly reported secondary outcome in VeriStrat studies.

Time to progression (TTP)TTP — time from treatment or randomization to documented disease progression (not including death), used in some studies as an outcome measure.

VeriStrat — MALDI‑MS–based proteomic classifier

Test methodologyVeriStrat — a MALDI‑MS–based proteomic classifier that categorizes patients as 'Good' or 'Poor' using identified mass spectral features and a trained algorithm.

Signature compositionThe classifier uses an 8‑peak/protein signature; several peaks have been identified as fragments of serum amyloid A protein 1, though full protein identities remain under investigation.

Regulatory/availability noteOffered as a laboratory‑developed test available through a single commercial laboratory under CLIA oversight per policy context.

MALDI‑MS — platform definition

Platform definitionMALDI‑MS — matrix‑assisted laser desorption ionization mass spectrometry, a mass spectrometry platform used to derive proteomic features for classifiers.

Use in proteomic assaysMALDI‑MS has been used to generate m/z features that form the basis of proteomic classifiers such as VeriStrat and other investigational tests.

Alternative MS methodsOther MS techniques (eg, surface‑enhanced laser desorption ionization/time‑of‑flight MS) have also been investigated for proteomic predictors, but remain investigational.

VeriStrat (expanded) — assay and signature

Expanded test descriptionVeriStrat (VS) — a commercially available serum/plasma MALDI‑MS–based proteomic test using an 8‑peak/protein signature (including fragments of serum amyloid A) and a classification algorithm that reports results as 'Good' or 'Poor'.

Clinical claimsVendor materials describe 'Good' as more likely to respond to standard care and 'Poor' as associated with aggressive disease and possible need for alternative strategies; however, specificity for malignant processes is not established.

Research contextLargest body of literature supports the VeriStrat algorithm, though constituent protein identities and biological specificity remain under investigation.

EGFR TKI relevance — therapies evaluated with VeriStrat

Commonly evaluated TKIsEGFR‑targeted TKIs most commonly evaluated in VeriStrat analyses include erlotinib and afatinib in the reviewed trials and cohorts.

Treatment contextsMany studies evaluated VeriStrat in patients treated with EGFR TKIs in populations unselected for EGFR‑sensitizing variants, a context not aligned with current guideline recommendations.

Implication for interpretationApplicability of VeriStrat predictive claims depends on contemporaneous use of EGFR‑variant testing and guideline‑directed sequencing of therapies.

VeriStrat coding reference — CPT 81538

Policy coding referenceCPT 81538 — Oncology (lung), mass spectrometric 8‑protein signature (VeriStrat‑type) is listed in the policy's coding section with the description including amyloid A and serum utilization.

Test label linkagePolicy text associates the 8‑protein/mass spectrometric signature with reported prognostic/predictive algorithm outputs ('good' vs 'poor').

Billing noteInclusion of CPT 81538 in coding is informational; coverage is determined by policy criteria and member contract.

EGFR testing — CPT 81235 reference

EGFR testing referenceEGFR testing (CPT 81235) — EGFR gene analysis for common variants is listed in the policy's coding section and recommended by guidelines for guiding EGFR‑targeted therapy.

Role relative to proteomicsMolecular EGFR testing remains the standard for identifying sensitizing variants to guide EGFR TKI use; proteomic assays do not replace gene variant testing.

Documentation practiceStudies evaluating VeriStrat often report EGFR variant status as a covariate; current clinical practice recommends routine EGFR testing in advanced nonsquamous NSCLC.

The policy references ongoing and published trials relevant to VeriStrat; among them, PROSE, EMPHASIS, TOPICAL, BR.21 analyses, LUX-Lung 8 analyses, and a noted ongoing observational trial (NCT03289780) are cited in the reference list.