DraftBlue Cross Blue Shield - Rhode IslandPolicy N/A

Medical Coverage Policy Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk Assessmentof ProstateCancer

Defines medical necessity criteria, prior authorization requirements, and CPT coding guidance for multiple genetic and protein biomarker tests used for prostate cancer diagnosis and rebiopsy decisions for BlueCHiP for Medicare and commercial products.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMedical Coverage Policy Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk Assessmentof ProstateCancer

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJul 1, 2020

Next Review Date

Key ActionObtain prior authorization via the online tool for participating providers for listed tests (PCA3, 4Kscore, ConfirmMDx, ExoDx, Apifiny, Mi-Prostate) before ordering.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes reported in this brief (has_material_change=false).

9Tests addressed in policy

6Tests requiring prior authorization (BlueCHiP for Medicare)

4Tests covered when criteria met (BlueCHiP for Medicare)

ManyNot medically necessary (Commercial Products)

Coverage Summary

This policy defines medical necessity criteria, prior authorization requirements, and CPT coding guidance for multiple genetic and protein biomarker tests used to help decide on initial or repeat prostate biopsy. It addresses specific assays (for example, Progensa PCA3, 4Kscore, ConfirmMDx, ExoDx Prostate IntelliScore, Apifiny, Mi-Prostate, phi, SelectMDx, Prostate Core Mitomics) and describes when BlueCHiP for Medicare considers particular tests covered if criteria are met. The overall coverage stance is mixed: some tests are covered for BlueCHiP for Medicare under defined clinical criteria, while many tests are considered not medically necessary for Commercial Products.

Key thresholds and quick facts

PSA range for 'moderately elevated'>3 and <10 ng/mL; or >4 and <10 ng/mL in men >75 years

ConfirmMDx prior biopsy tissue/core requirement>= 8 tissue cores previously collected (not a saturation >24 cores); remaining FFPE tissue from all cores must be available

ConfirmMDx minimum tissue volume>= 20 microns of prostate core tissue available (40 microns preferable)

Age threshold for EPI coverage (ExoDx Prostate IntelliScore)> 50 years

Age threshold for 4Kscore eligibility>= 45 years

Number of tests addressed in policy9

Medical Necessity Criteria

PCA3 (Progensa PCA3 Assay) - BlueCHiP for Medicare

PCA3 testing will be considered medically reasonable and necessary when ALL of the following are met:

ALL of the following

The subsequent prostate specific antigen (PSA) is rising
All biopsies in previous encounter(s) are negative for prostate cancer
The patient or physician wants to avoid repeat biopsy (avoid repeat 'watchful waiting' biopsy)

ref": "b1_0

title": "PCA3 (Progensa PCA3 Assay) - BlueCHiP for Medicare

Not Medically Necessary / Not Covered

For Commercial Products, the policy lists many of the referenced biomarker tests as not medically necessary. Tests specifically cited as not medically necessary for Commercial Products include kallikrein markers (4Kscore), Progensa PCA3, gene hypermethylation testing (ConfirmMDx), the Apifiny autoantibody panel, ExoDx Prostate IntelliScore (exosomal PCA3/ERG/SPDEF), and Mi-Prostate (MiPS). CPT/PLA codes associated with these tests (for example 81313, 81539, 81551, 0005U, 0021U, 0113U) are noted in the coding section but classified as not medically necessary for Commercial Products. BlueCHiP for Medicare coverage differs for several tests: when Medicare-specific medical necessity criteria are met, tests such as PCA3, 4Kscore, ConfirmMDx, and ExoDx may be considered medically necessary and covered.

Coding

Covered CPT / PLA codes (BlueCHiP for Medicare when criteria met)CPT|HCPCS|mixedCovered

81313	PCA3/KLK3 (prostate specific antigen 3) ratio (used to represent Progensa PCA3)
81539	Oncology (high-grade prostate cancer), biochemical assay of four proteins (total PSA, free PSA, intact PSA and hK2) plus clinical data (used for 4Kscore)
81551	Oncology (prostate), promoter methylation by real-time PCR of 3 genes (GSTP1, APC, RASSF1) (used for gene hypermethylation/ConfirmMDx)
0021U	Oncology (prostate), detection of 8 autoantibodies (Apifiny)
0113U	Oncology (prostate), measurement of PCA3 and TMPRSS2-ERG in urine and PSA in serum (Mi-Prostate/MiPS)
0005U	Oncology (prostate), gene expression by RT-PCR of ERG, PCA3, SPDEF; urine; algorithm reported as risk score (ExoDx Prostate IntelliScore)

Unlisted molecular pathology procedure (authorization required)CPT

81479

Unlisted molecular pathology procedure - use for tests without specific CPT code; requires prior authorization

Not medically necessary (Commercial Products)mixedNot Covered

81539	4Kscore (Kallikrein markers) - listed as not medically necessary for Commercial Products despite coverage for BlueCHiP for Medicare when criteria met
81313	PCA3 (Progensa PCA3 Assay) - listed as not medically necessary for Commercial Products
81551	Gene hypermethylation (ConfirmMDx) - listed as not medically necessary for Commercial Products
0021U	Apifiny autoantibody panel - listed as not medically necessary for Commercial Products
0005U	ExoDx Prostate IntelliScore (Exosome RNA exosomal PCA3/ERG/SPDEF) - listed as not medically necessary for Commercial Products
0113U	Mi-Prostate (MiPS) - listed as not medically necessary for Commercial Products

Prior Authorization

Unlisted CPT authorization

Use CPT 81479 (Unlisted molecular pathology procedure) when a test does not have a specific CPT/PLA code. Prior authorization is required when 81479 is used to determine what service is rendered and whether the service is covered or considered not medically necessary.

81479 — Use for tests without specific CPT code; prior authorization required to determine service coverage

Provider Actions

Prior Authorization

Prior authorization required (BlueCHiP for Medicare)

Prior authorization is required (BlueCHiP for Medicare) for the listed prostate biomarker tests. Participating providers must obtain authorization via the online prior authorization tool.

81313
81539
81551
0005U
0021U
0113U
81479
How to obtain: prior authorization obtained via the online tool for participating providers

Documentation Required

Background & Evidence

Background: Multiple genetic and protein biomarkers have been developed to improve selection of men for initial or repeat prostate biopsy. The document lists several FDA approvals and regulatory notes: the Progensa PCA3 assay received FDA premarket approval in February 2012 for aiding repeat biopsy decisions in men ≥50 with prior negative biopsies, and proPSA/phi received FDA premarket approval in June 2012 for men ≥50 with PSA 4–10 ng/mL and non-suspicious DRE. Many other tests are offered as laboratory-developed tests. Evidence conclusion: the policy states that the performance and clinical utility of many biomarkers vary by test and that, overall, evidence is insufficient for many biomarkers to demonstrate clinical utility for directing initial biopsy or rebiopsy decisions and to determine effects on health outcomes.

Definitions and evidence bullets

Definition - Confirmed PSAPSA verified after a few weeks under standardized conditions (no ejaculation, no manipulations, no urinary tract infections, no interfering medications)

FDA approval - Progensa PCA3Approved Feb 2012 to aid repeat biopsy decisions in men >=50 with one or more negative prostate biopsies

FDA approval - proPSA / phiApproved Jun 2012 as aid to distinguish prostate cancer vs benign conditions in men >=50 with PSA 4-10 ng/mL and non-suspicious DRE

Medicare Determinations

Type	Number	Name
LCD	L37798	4Kscore Test Algorithm
LCD	L37733	Biomarker Testing (Prior to Initial Biopsy) for Prostate Cancer Diagnosis
LCD	L36327	MolDX: ConfirmMDx Epigenetic Molecular Assay
NCD	A57605	MolDX: ConfirmMDx - Billing and Coding Article

Revision History

2020-07-01Policy effective

Policy effective date

2020-02-06Last reviewLatest

Policy last updated

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMedical Coverage Policy Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk Assessmentof ProstateCancer

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJul 1, 2020

Next Review Date

Key ActionObtain prior authorization via the online tool for participating providers for listed tests (PCA3, 4Kscore, ConfirmMDx, ExoDx, Apifiny, Mi-Prostate) before ordering.

SourceLink

On This Page

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4Kscore - BlueCHiP for Medicare

The 4Kscore test will be considered medically reasonable and necessary when ALL of the following are met and all algorithm components are present:

ALL of the following

Male aged 45 years or older
Initial or following negative prior biopsy with a confirmed moderately elevated PSA>3 and <10 ng/mL; or >4 and <10 ng/mL in men >75 years
PSA >3 and <10 ng/mL (or >4 and <10 ng/mL in men >75 years)
Shared decision making documented between ordering provider and beneficiary concerning 4Kscore testing
Documentation must be provided to the laboratory at ordering
Relative indications (ANY of the following may support testing)
- DRE suspicious for cancer
- Persistent and significant increase in PSA
- Other major risk factors (not exhaustive)
- Positive multiparametric MRI (if done)
- Ethnicity at higher risk for prostate cancer
- High-penetrance prostate cancer risk gene(s) per NCCN (if known)
- First-degree relative with prostate cancer
Relative contraindications (NONE of the following should be present unless medical record documents necessity)
- Less than a 10 year life expectancy
Benign disease not ruled out; PSA elevation should be verified under standardized conditions (no ejaculation, manipulations, urinary tract infections, interfering medications) before biopsy
Medical record must support necessity if only relative indications/contraindications present and must document shared decision making; documentation must be provided to the laboratory at ordering

ConfirmMDx - BlueCHiP for Medicare

ConfirmMDx is covered when ALL of the following are met:

ALL of the following

Male aged 40 to 85 years
Previous cancer-negative prostate biopsy within 24 months and patient is being considered for repeat biopsy due to persistent or elevated cancer-risk factors
Previous negative prostate biopsy must have collected a minimum of 8 tissue cores and not a saturation >24 cores; remaining FFPE tissue from all cores is available for testing>= 8 cores and <= 24 cores; remaining FFPE tissue available
ConfirmMDx minimum tissue cores collected previously
Previous histology does not include a diagnosis of prostate cancer or cellular suspicious for cancer (may include HGPIN, PIA, or glandular inflammation)
Minimum tissue volume criterion: 20 microns of prostate core tissue available (40 microns preferable)>= 20 microns (40 microns preferable)
ConfirmMDx minimum tissue volume
Patient is not managed by active surveillance for low-stage prostate cancer
Patient has not been previously tested by ConfirmMDx from the same samples or similar molecular test
Tissue was extracted via standard patterned core extraction (not TURP)

ExoDx Prostate IntelliScore (EPI) - BlueCHiP for Medicare

EPI is covered ONCE when ALL of the following are met:

ALL of the following

Male aged >50 years
Age for EPI coverage: > 50 years
Initial or prior negative biopsy with a confirmed moderately elevated PSA>3 and <10 ng/mL; or >4 and <10 ng/mL in men >75 years
PSA >3 and <10 ng/mL (or >4 and <10 ng/mL in men >75 years)
At least ONE of the following risk features
- DRE suspicious for cancer
- Persistent elevated PSA
- Positive multiparametric MRI (if done)
- Other major risk factors (e.g., first-degree relative with prostate cancer, high-risk ethnicity, high-penetrance gene per NCCN)
Relative contraindications (NONE should be present)
- Less than a 10 year life expectancy
Benign disease not ruled out; PSA verification and standardized conditions apply before biopsy

Apifiny and Mi-Prostate (MiPS)

May be considered medically necessary when BlueCHiP for Medicare medical necessity criteria in the Medical Necessity policy are used for review.

Review per the general Medical Necessity policy (related policy referenced)

Shared decision making documentation for 4Kscore

When ordering the 4Kscore (81539), document evidence of shared decision making between the ordering provider and the beneficiary in the medical record. Provide this supporting documentation to the laboratory at the time of ordering.

81539 — Document shared decision making in the medical record and provide documentation to the lab when ordering

Documentation Required

PSA verification prior to biopsy/testing

Verify that a PSA elevation is confirmed under standardized conditions before considering biopsy or ordering testing. A confirmed PSA requires verification after a few weeks with no ejaculation, no prostate manipulations, no urinary tract infection, and no interfering medications.

Confirmed PSA definition: verified after a few weeks under standardized conditions — no ejaculation, no manipulations, no urinary tract infections, no interfering medications

Billing Rule

Coverage variance by product

Coverage and medical necessity differ between BlueCHiP for Medicare and Commercial Products. Verify member-specific benefits in the applicable benefit booklet/evidence of coverage/subscriber agreement, and obtain prior authorization when required by the product.

Providers should verify member-specific benefits and coverage rules before testing
Obtain prior authorization when required by the member's product (use online tool for participating providers)