BCBSRI prostate biomarker Coverage Prior Auth

Coverage and Medical Necessity Criteria

MyProstateScore (MPS) medical necessity criteria

MyProstateScore (MPS) is considered medically necessary when ALL of the following are met:

Ordering limits: The test is ordered only once per year by a physician or other qualified health care professional (eg, NP, CNS, PA)1 per year

Confirmed PSA and age: Ordered prior to potential biopsy for men 45 years of age or older with confirmed PSA elevationage >=45

PSA elevation should be confirmed after a few weeks under standardized conditions (no ejaculation, manipulations, urinary tract infection) in the same laboratory before considering biopsy

Clinical features or risk factors supporting use: At least ONE of the following high-risk features: suspicious DRE (nodules, induration, or asymmetry); positive multiparametric MRI (PI-RADS 2–3) if available; prior atypical/suspicious biopsy findings (eg, cancer Grade Group 1, intraductal carcinoma, intraductal proliferation); ethnicity associated with higher prostate cancer risk; first-degree relative with prostate cancer; known high-penetrance prostate cancer risk gene per NCCN

Contraindications preventing testing: NONE of the following relative contraindications to prostate biopsy are present: active prostatitis currently on antibiotics; recent invasive treatment for benign prostatic disease or use of medications that influence serum PSA within the past 6 months; life expectancy <10 years or otherwise not a candidate for prostate cancer treatment

Authorization and ordering responsibility: Authorization must be obtained by the ordering physician via the online tool when required; laboratories or their representatives are not permitted to obtain authorization on behalf of the ordering physician

If a laboratory or third party obtains authorization, BCBSRI may deem this a policy violation and take action; unauthorized services may be denied and billed to the laboratory

The following tests are specifically mentioned in the policy as not covered or not medically necessary due to insufficient evidence to demonstrate improved net health outcomes: Apifiny, PanGIA Prostate, Prostate Core Mitomics Test (mitochondrial DNA variant testing), candidate gene panels, and single nucleotide variant testing for prostate cancer risk assessment. The policy describes the nature of these assays (for example, Apifiny measures an 8-autoantibody signature and PanGIA uses a nanosponge array with machine learning) and states that comparative studies and direct evidence of clinical utility are lacking for these tests.

Separately, some tests are addressed elsewhere in the policy as covered or conditionally covered when criteria are met (for example, Progensa PCA3 and ExoDx Prostate IntelliScore are listed as covered; Prostate Health Index requires filing with an Unlisted CPT and authorization). Providers should refer to the specific medical necessity criteria and authorization requirements for tests that are covered under defined conditions.

Coverage and payment are determined by the member's subscriber agreement, member certificate, and/or employer agreement; these member benefit documents supersede the provisions of this medical policy. For member-specific benefits and eligibility, providers must contact the provider call center.

If a service is a non-covered benefit under the member's plan, providers may not charge the member for that service unless the member was informed in advance and provided written agreement to accept responsibility for the charge. Refer to applicable participation agreements for additional billing restrictions.

Several named biomarker assays are discussed in the policy with brief coverage conclusions: Apifiny and PanGIA Prostate are described as investigational and are considered not covered/not medically necessary because evidence is insufficient to show clinical benefit; Apifiny is an 8-autoantibody serum algorithm and PanGIA is a urine-based nanosponge/machine-learning profile. Mitochondrial DNA variant testing (eg, Prostate Core Mitomics Test) and candidate gene panels are likewise considered not covered/not medically necessary for initial or repeat biopsy decisions due to limited comparative data and lack of demonstrated impact on clinical outcomes.

The policy also notes that some tests are addressed differently: Progensa PCA3 and ExoDx Prostate IntelliScore (EPI) are listed as covered; Prostate Health Index (phi) is covered but requires filing under an Unlisted CPT and authorization. Additionally, 4Kscore, ConfirmMDx, and SelectMDx may be considered medically necessary effective 07/01/2025 when online authorization criteria for participating providers are met.

For coding, the policy highlights that certain CPTs (for example, 0228U for PanGIA-style testing and 86316 when filed with specified ICD-10 codes) are restricted or not covered in particular situations; consult the coding section for exact filing guidance.

Coding and Billing

Covered / addressed CPT codesCPT

0005U	ExoDx Prostate IntelliScore (Oncology (prostate) gene expression by real-time RT-PCR of 3 genes (ERG, PCA3, and SPDEF), urine, algorithm reported as risk score profile)
81313	Progensa PCA3 assay (PCA3/KLK3 ratio)
0021U	Apifiny (detection of 8 autoantibodies), multiplexed immunoassay and flow cytometry serum, algorithm reported as risk score
0113U	MyProstateScore (measurement of PCA3 and TMPRSS2-ERG in urine and PSA in serum), algorithm reported as risk score
0228U	PanGIA Prostate (multianalyte molecular profile by photometric detection of macromolecules adsorbed on nanosponge array slides with machine learning, urine)
81479	Unlisted molecular pathology procedure (used for tests without specific CPT e.g., Prostate Health Index (phi) in some filings)
86316	Immunoassay for tumor antigen, other antigen, quantitative (eg, CA 50, 72-4, 549), each
81539	4Kscore (multimarker blood test)
81551	ConfirmMDx
0339U	SelectMDx

Not covered CPT codesCPTNot Covered

0021U	Oncology (prostate), detection of 8 autoantibodies (Apifiny), multiplexed immunoassay and flow cytometry serum, algorithm reported as risk score — listed as not covered when filed for Medicare Advantage and not medically necessary for Commercial Products
0228U	Oncology (prostate), multianalyte molecular profile by photometric detection of macromolecules (PanGIA Prostate) — noted in not covered context
86316	Immunoassay for tumor antigen, other antigen, quantitative (eg, CA 50, 72-4, 549), each — listed as not covered when filed with certain ICD-10-CM codes

ICD-10-CMICD-10

C61	ICD-10-CM code for prostate cancer referenced in coding section

PSA ranges and thresholds for phi and MPS

phi (Prostate Health Index) labeled PSA rangePSA 4–10 ng/mL per FDA labeling for phi in men age 50+ with non-suspicious DRE

MPS — lower PSA references used in clinical criteriaReferences to moderately elevated PSA thresholds (eg, >3 ng/mL) used in decision-making for MPS

MPS — traditional PSA biopsy thresholds citedPSA thresholds of ~4 ng/mL and 10 ng/mL are mentioned in MPS clinical criteria context

Provider Requirements and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Medicare Advantage plans and is recommended for Commercial products. Participating ordering physicians must obtain prior authorization via the insurer's online tool for the specified tests (for example, MyProstateScore 0113U).

Prior authorization required for Medicare Advantage; recommended for Commercial.
MyProstateScore (0113U) requires prior authorization.

Note

Verify Member Eligibility and Benefits

Verify member-specific benefits and eligibility before providing services. Coverage and payment are determined by the member’s benefit plan and the member certificate (subscriber agreement or employer agreement) — those documents govern. Contact the provider call center for member benefit verification.

Benefits and eligibility determined by the member’s certificate/subscriber agreement — those documents supersede this policy.
Providers should call the provider call center to confirm member-specific benefits and eligibility prior to ordering services.

Background and Scope

Prostate cancer spans a spectrum from indolent to aggressive disease; this heterogeneity creates a clinical need to distinguish men who truly require biopsy and potential treatment from those who can be safely observed. Biomarker assays—both urinary and blood-based—are intended to improve risk stratification and refine selection for initial or repeat prostate biopsy, thereby reducing unnecessary procedures and harms.

FDA-cleared tests (for example, the PCA3 assay and the Prostate Health Index) have specific labeled indications and defined PSA ranges in their approvals, whereas many newer assays have limited comparative evidence. The policy emphasizes that while some biomarkers are associated with detection of prostate cancer or aggressive disease, direct evidence that using these tests changes physician decision-making or improves long-term clinical outcomes is limited for several tests.

Consequently, the policy applies differentiated coverage: certain established assays are covered when clinical criteria are met, some tests require authorization or special coding, and others (including several newer molecular or genomic assays) are considered not covered or not medically necessary pending stronger evidence of clinical utility.

Test Definitions and Short Descriptions

ExoDx Prostate (EPI) — assay and reporting

Test descriptionUrine-based 3-gene exosome expression assay measuring ERG, PCA3, and normalized to SPDEF reported as a risk score

Sample and collection noteAssay performed on urine; does not require a digital rectal exam (DRE) for collection

Intended useUsed to predict risk of high-grade prostate cancer and inform biopsy decisions in men with elevated PSA (literature supports use for PSA 2–10 ng/mL in some studies)

ReportingResult reported as an algorithm-derived risk score (IntelliScore/EPI) based on exosomal RNA expression of the three genes

Progensa PCA3 — FDA-approved use

FDA-approved indicationProgensa PCA3 is FDA-approved to aid the decision for repeat biopsy in men 50 years or older with one or more prior negative prostate biopsies when a repeat biopsy is being considered

References and Related Policies

Selected guideline and literature sources cited in the policy include national guidance and peer-reviewed studies underpinning biomarker evaluation and prostate cancer screening recommendations (for example, U.S. Preventive Services Task Force guidance). The references section lists multiple primary studies, systematic reviews, and national guidance documents that were reviewed in developing the policy.

Related policies and documents to review alongside this policy include: Genetic Testing Services, Biomarker Test Mandate, Proprietary Laboratory Analyses (PLA), and policies addressing genetic test medical necessity and unlisted procedures. These related policies provide additional context on coding, laboratory filing practices, and eligibility determinations relevant to molecular and genetic testing for prostate cancer.

OpenPayer

Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk Assessment of Prostate Cancer