CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk

This policy governs coverage and medical necessity determinations for genetic and protein biomarker tests used to aid diagnosis of prostate cancer and assess cancer risk for BlueCHiP for Medicare and Commercial products under Blue Cross Blue Shield - Rhode Island.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyGenetic and Protein Biomarkers for the Diagnosis and Cancer Risk

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJul 1, 2019

Next Review DateN/A

Key ActionObtain prior authorization for BlueCHiP for Medicare (recommended for Commercial) via the online tool; use unlisted molecular pathology code 81479 when appropriate.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

07/01/2019policy effective date

4Kscore, phiMedicare coverage examples

Multipletests listed

~27literature refs

Coverage and Medical Necessity Determinations

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Coverage determinations

Covered when meeting the product‑specific determinations below:

BlueCHiP for Medicare - Covered without prior authorization: 4Kscore Test and Prostate Health Index (phi) are considered medically necessary and covered without prior authorization (effective 12/1/2018).

BlueCHiP for Medicare - Not covered / not medically necessary: The following genetic and protein biomarker tests are not covered for BlueCHiP for Medicare because evidence is insufficient to determine effects on health outcomes: TMPRSS2:ERG fusion gene assays (eg, MiPS); HOXC6 and DLX1 testing (eg, SelectMDx); gene hypermethylation testing (eg, ConfirmMDx); mitochondrial DNA variant testing (eg, Prostate Core Mitomics Test); candidate gene panels; and single nucleotide variant testing for cancer risk assessment of prostate cancer.

Commercial Products - Not medically necessary: For Commercial products the following are considered not medically necessary due to insufficient evidence: kallikrein marker tests (eg, 4Kscore), Prostate Health Index (phi), PCA3 testing (eg, Progensa PCA3), HOXC6 and DLX1 testing (eg, SelectMDx), TMPRSS2:ERG fusion gene assays (eg, MiPS), mitochondrial DNA variant testing (eg, Prostate Core Mitomics Test), gene hypermethylation testing (eg, ConfirmMDx), candidate gene panels, and single nucleotide variant testing for cancer risk assessment of prostate cancer.

Single nucleotide variant testing for cancer risk assessment of prostate cancer is not covered / not medically necessary. The policy states that evidence is insufficient to determine the effects of single nucleotide variant testing on health outcomes for prostate cancer, and therefore this testing is excluded for both BlueCHiP for Medicare and Commercial products.

Coverage and benefits are determined by the member's subscriber agreement, member certificate, and/or employer agreement, which supersede this medical policy. For member-specific benefits and eligibility, contact the provider call center. If services are determined to be not medically necessary or are non-covered benefits, a provider may not charge the member unless the member was informed and provided written agreement in advance to continue at their own expense.

For Commercial products this policy identifies multiple named biomarker tests as not medically necessary due to insufficient evidence. Examples listed include: 4Kscore Test (kallikrein markers), Prostate Health Index (phi), PCA3 (eg, Progensa PCA3 Assay), SelectMDx (HOXC6 and DLX1), MiPS (TMPRSS2:ERG fusion gene assays), Prostate Core Mitomics Test (mitochondrial DNA variant testing), ConfirmMDx (gene hypermethylation testing), and various candidate gene panels.

When a service is determined to be not medically necessary or otherwise non-covered, the claim may be denied and the provider should follow member eligibility rules. Providers may not bill the member for services determined to be not medically necessary unless the member was informed and provided written consent in advance to accept financial responsibility.

Coding and Billing Guidance

Covered CPT Codes (BlueCHiP for Medicare)CPTCovered

81313

PCA3/KLK3 (prostate specific antigen 3 [non-protein coding] / kallikrein-related peptidase 3 [prostate specific antigen]) ratio (eg, prostate cancer)

Covered CPT Codes (BlueCHiP for Medicare)CPTCovered

81539

Oncology (high-grade prostate cancer), biochemical assay of four proteins (total PSA, free PSA, intact PSA and human kallikrein 2 [hK2]), plus age, digital rectal examination status, and no history of positive prostate biopsy, prognostic algorithm reported as probability score

Not covered / Not medically necessary CodesCPTNot Covered

81551

Oncology (prostate), promoter methylation profiling by real-time PCR of 3 genes (GSTP1, APC, RASSF1), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as likelihood of prostate cancer detection on repeat biopsy

Unlisted CPT requiring authorizationCPT

81479

Unlisted molecular pathology procedure

Coding / CMS guidancemixed

MolDX: PROGENSA PCA3

CMS Local Coverage Article referenced for PROGENSA PCA3 assay and billing guidelines

phi indication: PSA range and patient selection

PSA rangeTotal PSA 4.0–10.0 ng/mL

Age and examMen 50 years and older with a non‑suspicious digital rectal exam (DRE)

Intended usePhi indicated as an aid to distinguish prostate cancer from benign prostatic conditions in this population

Specimen requirementBlood serum immunoassays for total PSA, free PSA and [-2]proPSA are required to calculate phi

Provider Requirements and Administrative Actions

Prior Authorization

Prior Authorization Required

Prior authorization is required for BlueCHiP for Medicare and is recommended for Commercial products. Participating providers must obtain authorization via the payer's online tool.

Applies to BlueCHiP for Medicare (required) and Commercial (recommended).
Obtain via the online prior authorization tool for participating providers.

Billing Rule

Unlisted CPT Authorization Risk

Use of unlisted CPT codes (eg, 81479 for unlisted molecular pathology procedure) may require prior authorization so the payer can identify the specific service rendered and determine coverage/medical necessity. When an unlisted CPT is billed, include supporting documentation that describes the procedure/test performed.

Unlisted molecular pathology CPT 81479: authorization required for BlueCHiP for Medicare and Commercial products.
Provide detailed clinical and technical documentation when billing unlisted CPT codes to allow coverage determination.

Documentation Required

Specimen and Clinical Documentation

Submit appropriate specimen handling information and clinical documentation with molecular and laboratory-developed tests. For example, PCA3 requires first urine collected after a DRE; phi and PSA-related assays require documentation of PSA ranges and DRE status. Labs must be CLIA-certified for high-complexity testing.

PCA3 (Progensa): first-catch urine collected after attentive DRE.
phi and PSA assays: document total PSA, free PSA, and DRE status; indicate patient age and PSA range when applicable.
Laboratory-developed tests must be performed by CLIA-certified high-complexity laboratories.

Note

Benefits and Eligibility Determination

Benefits and eligibility are determined by the member's subscriber agreement, member certificate, and/or employer agreement; those documents supersede this policy. For member-specific benefit questions, contact the provider call center.

Coverage decisions may vary by contract; verify benefits and eligibility prior to service.
If a service is determined non-covered or not medically necessary, the member/provider may be financially liable only if the member was informed and provided written consent in advance.

Denial Risk

Financial Liability When Service Is Non‑Covered

If a service is not covered or is determined not medically necessary, denials may result in financial liability for the member or provider unless prior written consent was obtained from the member.

Providers should confirm coverage and obtain necessary authorizations to avoid unexpected member liability.

Note

Provider Action — General

When prior authorization is required or recommended, check related policies for specific code and test references and follow any step-therapy or other administrative requirements specified there.

See Related Policies section for additional authorization details and any test-specific requirements.

Definitions and Test Descriptions

Gleason score / grading

DefinitionHistologic grading system summing primary and secondary architectural patterns to produce a Gleason score

Score interpretationGleason score ≤6 = low-grade (usually slow growing); 7 = intermediate grade; 8–10 = high-grade (more aggressive)

BasisScore equals sum of primary and secondary patterns, each graded 1 (well differentiated) to 5 (poorly differentiated)

Clinical correlationScores correlate with tumor aggressiveness and inform prognosis and management decisions

Prostate Health Index (phi)

What phi isA calculated Prostate Health Index (phi) combining total PSA, free PSA and [-2]proPSA into a single score

CalculationPhi algorithm: ([-2]proPSA / free PSA) x sqrt(total PSA)

Intended populationMen age 50 years and older with total PSA 4.0–10.0 ng/mL and a non‑suspicious DRE

Clinical purposeUsed as an aid to help distinguish prostate cancer from benign prostatic conditions and reduce unnecessary biopsies

PCA3 / PROGENSA PCA3 Assay

Test typeUrine‑based molecular assay measuring PCA3 mRNA (PROGENSA PCA3) performed on first‑catch urine after attentive DRE

Regulatory/coding guidanceProgensa PCA3 is FDA‑approved; CMS MolDX Local Coverage Article (MolDX: PROGENSA PCA3) referenced for coding and billing

Clinical roleUsed to aid decision making for repeat prostate biopsy by improving specificity over PSA alone

PSA (prostate-specific antigen)

BiomarkerProstate‑specific antigen (PSA) is a blood biomarker commonly used for prostate cancer screening and diagnosis

Use in testsPSA (total and free) is a component of multiple derived assays (eg, phi, 4Kscore) used to estimate cancer risk

Evidence and referencesMultiple studies and reviews are cited in support of PSA use and thresholds (see referenced literature and SEER/CMS sources)

Threshold contextHistorical screening thresholds include 4.0 ng/mL as a common cutpoint examined in the literature

OpenPayer

Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk

Coverage and Medical Necessity Determinations

Coding and Billing Guidance

Provider Requirements and Administrative Actions

Background and Policy Scope

Definitions and Test Descriptions