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ModifiedProvidence Health PlanPolicy 96

Protein Biomarker and Genetic Testing for the Prostate

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This policy describes and evaluates multiple urine-, blood-, and tissue-based protein biomarker and genetic assays used for detection, risk stratification, prognosis, and treatment decision-making in prostate cancer; it governs coverage and clinical use criteria for Providence Health Plan members and providers.

Policy Summary

PayerProvidence Health Plan

PolicyProtein Biomarker and Genetic Testing for the Prostate

Policy CodePolicy 96

Change TypeCriteria expandedcodes addedrepeat-testing criterion added

Effective DateJul 1, 2026

Last ReviewJul 1, 2025

Next Review DateApr 1, 2027

Key ActionObtain prior authorization when ordering listed molecular/proprietary prostate assays or when using unlisted codes; include the specific test code and documentation showing how results will change management.

SourceLink

POLICY UPDATE CHANGES

CPT code added for PanGIA Prostate testing.

Criterion added for repeat testing.

Criteria expanded to include additional NCCN recommended tests.

PanGIA Prostate added to list of non-covered panels.

Interim updates made to medical necessity criteria and code set updates across multiple quarters.

1CPT code added for PanGIA Prostate

1Repeat testing criterion added

expandedCriteria expanded (NCCN)

multipleCode set/interim updates documented

~20 assays describedNamed assays referenced

Coverage Criteria and Policy Scope

Selective coverage when test will change management

Covered when ALL of the following conditions are met:

Selective use conditions: Tissue-based or protein biomarker genomic assays (e.g., Decipher, Oncotype DX Prostate, Prolaris) are considered when both standard clinical and pathologic risk stratification is insufficient to inform a management decision AND the assay result is likely to change management (for example, decision between active surveillance versus definitive treatment, or adjuvant versus salvage therapy post-prostatectomy).N/A

Reflects AUA/ASTRO/SUO and ASCO guidance endorsing selective (not routine) use.

Acceptable tests / clinical contexts: Decipher may be used to estimate 5-year metastasis risk after radical prostatectomy and as an adjunct on biopsy specimens for selected NCCN risk categories; Oncotype DX Prostate and Prolaris may be used to inform decisions about active surveillance versus treatment in patients with very low, low, or favorable/intermediate risk disease when results would influence management.N/A

Use in contexts where result will alter management is required.

Policy Summary

PayerProvidence Health Plan

PolicyProtein Biomarker and Genetic Testing for the Prostate

Policy CodePolicy 96

Change TypeCriteria expandedcodes addedrepeat-testing criterion added

Effective DateJul 1, 2026

Last ReviewJul 1, 2025

Next Review DateApr 1, 2027

SourceLink

On This Page

Evidence & documentation: Ordering clinician must document that (1) standard clinicopathologic factors were evaluated (PSA, Gleason/grade group, clinical stage, DRE), (2) the test is expected to inform a specific management decision, and (3) patient life expectancy and NCCN risk grouping were considered.N/A

Documentation supports medical necessity and prior authorization review.

Updated coverage criteria (summary)

Summary of recent operational and criteria updates:

Policy update items: CPT code added for PanGIA Prostate testing; criterion introduced for repeat testing (7/2024); interim expansions to include additional NCCN‑recommended tests (8/2024); multiple quarterly code set updates through Q2 2025 and interim medical necessity adjustments.

See revision history for effective dates and impacted tests.

Revision-driven coverage changes

Revision highlights that affect coverage rules and operational handling:

Revision-driven changes: Added CPT code(s) for PanGIA Prostate; added a repeat testing criterion (first introduced 7/2024); criteria expanded to include additional NCCN‑recommended tests (interim updates 8/2024); interim update to medical necessity criteria noted in Q2 2025.

These changes may affect prior authorization and claim adjudication.

Medical necessity criteria (updates)

Updates to medical necessity criteria summarized below (operational):

Medical necessity updates: Interim and annual reviews (Q3 2024, 8/2024 interim, Q2 2025) resulted in: expansion to include additional NCCN‑recommended tests, addition of a repeat testing criterion, and multiple code set updates; 5/2025 annual review recorded no changes to codes or criteria.

Providers should confirm current effective policy version and code list before ordering.

The Progensa® PCA3 assay is a post-DRE urine test that reports a PCA3 score to estimate the probability of a positive repeat prostate biopsy. It is intended for men ≥50 years who have had one or more prior negative prostate biopsies and is to be used in conjunction with serum PSA and other clinical risk indicators to help decide whether to pursue repeat biopsy. The Progensa PCA3 assay is not indicated for patients with atypical small acinar proliferation on their most recent biopsy and should be interpreted as an adjunct to, not a replacement for, standard clinical risk assessment. (Progensa PCA3: [[chunk 23]]; evidence reviews: [[chunk 45]])

Other proposed molecular urine- or blood-based assays (for example, EpiScore, NeoLAB Prostate Liquid Biopsy, Mi-Prostate Score, and PanGIA Prostate) have no identified clinical utility studies

Several tests evaluated in the evidence review have very low or insufficient-quality evidence for clinical utility and therefore are not supported for broad clinical use. Examples include the Oncotype DX AR-V7 Nucleus Detect test (evidence judged very low and lacking clinical utility studies), Prolaris (very-low overall evidence and insufficient demonstration of outcome benefit), and ProMark (very-low evidence without clinical utility data). Use of these assays may be associated with a high risk of denial if clinical utility is not documented. (Oncotype AR-V7: [[chunk 55]]; Prolaris: [[chunk 59]]; ProMark: [[chunk 61]])

If an unlisted code is submitted for services addressed in this policy, the claim will be reviewed for medical necessity, correct coding, and pricing; where an unlisted code is submitted for a service that is non-covered under this policy it will be denied as not covered. To avoid post-service denial when submitting unlisted codes for potentially covered services, prior authorization is recommended. (Coding and denial guidance: [[chunk 79]])

The PanGIA Prostate multi-analyte urine panel is explicitly described as having a current lack of evidence on clinical value and has been placed on the policy's list of non-covered panels. A CPT code for PanGIA testing was added in prior revisions, but despite that addition the panel itself is listed as non-covered in the document excerpt. Providers should note PanGIA Prostate is treated as a non-covered panel in this policy. (PanGIA lack of evidence: [[chunk 22]]; placement on non-covered list and revision history: [[chunk 90]], [[chunk 88]])

Within the provided excerpt there are no additional explicit test exclusions enumerated beyond those discussed (for example, PanGIA placement on the non-covered list). Revision notes reference code and criteria updates but do not list further test-specific exclusions in these chunks. (No explicit exclusions in excerpt: [[chunk 116]]; annual review note: [[chunk 148]])

The excerpted policy sections do not enumerate further explicit exclusions for molecular or protein biomarker assays. Revision history entries document multiple code-set and medical necessity updates, but specific new exclusion language is not present in these chunks. (No explicit exclusions listed in this excerpt: [[chunk 148]]; revision history/code updates: [[chunk 164]])

Revision history for this policy notes an annual review in 5/2025 stating 'No changes to codes or criteria'. This indicates that as of the 5/2025 annual review the policy authors documented no modifications to the codes or coverage criteria in that specific update. (Revision history entries: [[chunk 152]]; related code-set update notes: [[chunk 164]])

The policy reviews a range of molecular and protein biomarker assays used for detection, triage, prognosis, and treatment decision-making — including 4Kscore, ConfirmMDx, Progensa PCA3, PHI, SelectMDx, ExoDx, Decipher, Oncotype DX GPS/AR-V7, Prolaris, and ProMark. Across tests, evidence reviewers frequently found low- or very-low-quality evidence and often concluded that clinical utility was insufficient or inconclusive; guideline recommendations support selective, not routine, use in specified clinical contexts. (Evidence summaries and individual test reviews: [[chunk 38]], [[chunk 42]], [[chunk 45]], [[chunk 47]], [[chunk 49]], [[chunk 52]], [[chunk 53]])

Routine or indiscriminate ordering of molecular and proteomic prostate assays is not supported by the evidence reviewed. Systematic reviews and test assessments repeatedly noted that although some assays may change biopsy or treatment recommendations, there is insufficient high-quality evidence that such changes improve long-term patient outcomes; therefore use should be limited to situations where guideline-directed selective use would influence management. (Evidence on limited clinical utility and guideline context: [[chunk 55]], [[chunk 59]], [[chunk 68]])

Historical revision summaries document a change in denial terminology from 'investigational' to 'not medically necessary' for non-covered services in earlier updates. These entries reflect an evolution in policy wording for non-covered assays in prior revisions. (Revision history documenting wording changes: [[chunk 87]], [[chunk 88]], [[chunk 89]])

The chunks provided do not contain a formal, explicit 'not medically necessary' determination paragraph for individual tests within this excerpt; however, the policy's interim updates and revision history indicate that some panels or uses may be classified as not medically necessary under updated criteria or when evidence is insufficient. Providers should consult the full policy for formal NMN statements. (No explicit NMN statements in these chunks; interim updates noted: [[chunk 96]], [[chunk 116]])

An interim medical necessity update referenced in the revision history (Q2 2025) implies that some tests or uses could be categorized as not medically necessary under the revised criteria. The excerpt does not list specific NMN conditions but flags that interim criteria changes may affect coverage determinations. (Interim update and interim medical necessity reference: [[chunk 116]], [[chunk 152]])

Not specified in the provided excerpt. The chunks reviewed focus on test descriptions, evidence summaries, coding, and revision history; specific content referenced by this planner item is not present in these fragments. (See revision history/code-set notes: [[chunk 164]])

Covered Indications and Clinical Uses

Prognostic use post-biopsy or post-prostatectomy to inform management

Covered prognostic use — considered when ALL of the following are met:

Post-biopsy/post-prostatectomy prognostic testing: Prognostic genomic classifiers (for example, Decipher) are covered when results are intended to inform a specific post-diagnostic or post-prostatectomy management decision (e.g., selection for active surveillance vs treatment; adjuvant versus salvage radiation) and when standard clinicopathologic factors alone are insufficient to resolve management.N/A

Decipher estimates 5‑year metastasis risk after radical prostatectomy and is accepted in specified NCCN biopsy risk categories.

Acceptable tests: Decipher (post-prostatectomy and selected biopsy contexts), Oncotype DX Prostate (to inform active surveillance versus treatment), and Prolaris (to assist 10‑year prognosis) may be considered under the conditions above.N/A

Coverage contingent on demonstration that result will change management.

Prognostic testing to inform metastasis risk or treatment decisions (Decipher, Oncotype DX GPS)

Prognostic testing to inform risk of metastasis or to influence post-diagnostic treatment decisions is considered when the following apply:

General rule: Prognostic assays (e.g., Decipher, Oncotype DX Genomic Prostate Score) may be used as adjuncts when the clinician documents that the test result will influence a specific treatment recommendation or surveillance plan and when clinicopathologic data alone are insufficient to make that decision.N/A

Evidence shows potential prognostic value but insufficient high-quality data that use improves long-term outcomes; use should be selective per guideline recommendations.

Test-specific context: Decipher: may estimate 5‑year metastasis risk post-prostatectomy and may be used on biopsy tissue in selected NCCN risk categories. Oncotype DX GPS: intended to predict tumor aggressiveness to assist decisions between active surveillance and treatment. Prolaris: intended to assist 10‑year prognosis and post-prostatectomy biochemical recurrence risk assessment (not validated for patients with PSA >100 ng/mL or those receiving pre-biopsy adjuvant hormone/radiation therapy).N/A

Documentation that results will alter management is required.

Prebiopsy triage or decision-making for biopsy (4Kscore, ConfirmMDx, PCA3/Progensa, PHI, SelectMDx, ExoDx)

Prebiopsy triage tests may be considered selectively when ALL of the following conditions are met:

Prebiopsy triage coverage conditions: Urine- or blood-based detection/triage assays (e.g., 4Kscore, ConfirmMDx, Progensa PCA3, PHI, SelectMDx, ExoDx) may be considered when: (1) PSA and clinical evaluation alone leave uncertainty about the need for initial or repeat biopsy, (2) test use is expected to alter the decision to proceed with biopsy, and (3) documented counseling and follow-up plans are available if biopsy is deferred.N/A

Studies report changes in biopsy rates but lack comparative trials showing improved clinical outcomes; use should be selective and documented.

Intended PSA ranges and prior-biopsy status: Follow intended test indications where specified (for example, ExoDx intended for PSA 2–10 ng/mL; PHI commonly used in PSA 4–10 ng/mL ranges) and consider prior negative biopsy status for PCA3/Progensa testing.PSA ranges per test

See coding/definitions for test‑specific intended PSA ranges.

Hereditary prostate cancer evaluation using multi-gene panels when clinically indicated

Hereditary prostate cancer panel testing is covered when ALL of the following are satisfied:

Hereditary panel coverage: Multi-gene hereditary prostate cancer panels (for example, the 23-gene panel reported under CPT/HCPCS 0475U) are covered when there is clinical indication such as a relevant personal or family history of prostate or related cancers that meets established criteria and when results would change management (surveillance, cascade testing, or therapeutic decisions).N/A

The document describes the 23‑gene panel (0475U) but does not list explicit family-history thresholds in this excerpt; ordering clinicians should document clinical indications and family history.

Reporting requirements: Panel reporting should include pathologic (likely pathogenic/pathogenic) variants and provide a genetic risk score when available to inform clinical decision-making.N/A

Refer to laboratory and genetic counseling requirements per plan when available.

Hereditary prostate cancer evaluation via multi-gene panel and reporting of pathologic mutations with a genetic risk score

Coverage conditions for hereditary panel reporting and risk scoring:

Panel and reporting: When a hereditary prostate cancer multi-gene panel is ordered (e.g., 0475U), the laboratory report must list pathologic mutations detected and provide the panel‑derived genetic risk score where available; testing is considered when results will guide management or familial risk assessment.N/A

Specific coverage thresholds for genetic risk score interpretation are not provided in this excerpt.

Interim update expanded criteria to include additional NCCN recommended tests

Interim updates expanded coverage in accordance with NCCN recommendations:

Interim expansion summary: Interim update (8/2024) and subsequent revision notes expanded criteria to include additional NCCN‑recommended tests; these interim changes are reflected in code set updates and revision history entries through Q2 2025.

Specific individual tests added under the expansion are not enumerated in this excerpt; providers should verify the current approved test list.

Inclusion of additional NCCN recommended tests

Inclusion of additional NCCN‑recommended tests noted in revision history:

Coverage expansion: Revision history documents criteria expansion to align with additional NCCN‑recommended tests (noting interim updates in 8/2024 and code set updates thereafter).

The excerpt does not list explicit new test names or clinical indications added; confirm current policy for details.

Additional NCCN-recommended tests added to coverage criteria (8/2024 interim)

Additional NCCN‑recommended tests were operationally added to coverage criteria as noted in revision entries:

8/2024 interim expansion: Interim update (8/2024) expanded coverage criteria to include additional NCCN‑recommended tests; subsequent code set and medical necessity updates documented through Q2 2025.

Providers must refer to the current policy version to determine which NCCN‑recommended tests are included.

Criteria expansion to include additional NCCN recommended tests noted in interim updates

Criteria expansion logged across multiple interim updates — operational note:

Criteria expansion note: Document revision history records expansion to include additional NCCN‑recommended tests, repeat testing criterion addition, and multiple CPT/code set updates; specific test-level criteria resulting from these expansions are not provided in the excerpt.

Confirm current policy for detailed eligibility and test lists prior to ordering.

Non-covered Tests and Panels

PanGIA Prostate and several other newer or proposed assays lack identified clinical utility studies and therefore are listed as not covered or not supported in this policy excerpt. Specific assays called out as lacking demonstrated clinical utility in the not-covered sections include EpiScore, NeoLAB Prostate Liquid Biopsy, PanGIA Prostate, and Mi-Prostate Score; other tests with insufficient evidence (for prognostic or predictive use) include Oncotype DX AR-V7 Nucleus Detect, Prolaris, and ProMark. The evidence reviews across these assays consistently rated clinical utility as insufficient or very low. (PanGIA and other assays lacking clinical utility studies: [[chunk 22]], [[chunk 50]]; AR-V7, Prolaris, ProMark evidence: [[chunk 55]], [[chunk 59]], [[chunk 61]])

The policy specifies that several proposed molecular assays for biopsy decision-making have no identified clinical utility studies; examples listed include EpiScore, NeoLAB Prostate Liquid Biopsy, PanGIA Prostate, and Mi-Prostate Score. In the absence of clinical utility evidence, these assays are not supported for use in initial or repeat biopsy decision-making. (No clinical utility studies identified: [[chunk 50]]; PanGIA description: [[chunk 22]])

Specific assays evaluated that have insufficient or very-low-quality evidence for clinical utility include the Oncotype DX AR-V7 Nucleus Detect test (no clinical utility studies identified), Prolaris (overall evidence rated very low with insufficient demonstration of outcome benefit), and ProMark (very-low evidence and no clinical utility studies). These tests are not supported for routine clinical decision-making based on the current evidence synthesis. (Evidence summaries: [[chunk 55]], [[chunk 59]], [[chunk 61]])

One listed code/test—0550U—is explicitly marked as TERMED 1/1/2026 in the billing/coding section of the policy excerpt. Providers should note the retirement date for this specific code when submitting claims. (Billing/coding termination note: [[chunk 74]]; coding table reference: [[chunk 73]])

The PanGIA Prostate panel is explicitly listed among non-covered panels in the policy revision history and the PanGIA test description notes a lack of evidence on clinical value, supporting its placement on the non-covered list. Providers should treat PanGIA Prostate as a non-covered panel per this excerpt. (Panel non-coverage and description: [[chunk 90]], [[chunk 22]])

Within the provided excerpt there are no additional explicit not-covered genetic tests enumerated beyond those already noted (for example, PanGIA). The document indicates some panels are non-covered but does not list other specific genetic tests as not covered in these chunks. (No explicit not-covered genetic tests identified in these chunks: [[chunk 116]])

Billing Codes and Code Set Updates

Billing / Proprietary test codesCPT | HCPCS | mixed

0133U	Oncology, prostate cancer, mRNA expression assay of 12 genes..., RT-PCR test utilizing blood plasma and/or urine, algorithm reported as risk score
0228U	Oncology (prostate), multianalyte molecular profile by photometric detection... first morning voided urine, algorithm reported as likelihood of prostate cancer
0339U	Oncology (prostate), mRNA expression profiling of HOXC6 and DLX1, RT-PCR, first-void urine, algorithm reported as probability of high-grade cancer
0343U	Oncology (prostate), exosome-based analysis of 442 small noncoding RNAs by RT-qPCR, urine, reported as molecular evidence of risk
0359U	Oncology (prostate cancer), analysis of all PSA structural isoforms by phase separation and immunoassay, plasma, algorithm reports risk of cancer
0403U	Oncology (prostate), mRNA gene-expression profiling of 18 genes, first-catch urine, algorithm reported as percentage likelihood of detecting clinically significant prostate cancer
0424U	Oncology (prostate), exosome-based analysis of 53 sncRNAs by RT-qPCR, urine, reported as no/low/moderate/elevated risk of prostate cancer
0433U	Oncology (prostate), 5 DNA regulatory markers by quantitative PCR, whole blood, algorithm including PSA, reported as likelihood of cancer
0475U	Hereditary prostate cancer-related disorders, genomic sequence analysis panel using NGS, Sanger sequencing, MLPA, array CGH; evaluation of 23 genes and duplications/deletions when indicated
0495U	Oncology (prostate), analysis of circulating plasma proteins (tPSA, fPSA, KLK2, PSP94, GDF15), germline polygenic risk score (60 variants), clinical info, algorithm reported as likelihood of detecting clinically significant prostate cancer

1–10 of 11
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Prostate-related molecular and multianalyte CPT/HCPCS codesCPT/HCPCS

0424U	Exosome-based analysis of 53 small noncoding RNAs (sncRNAs) by RTqPCR, urine, reported as no molecular evidence, low-, moderate- or elevated-risk of prostate cancer.
0433U	Oncology (prostate), 5 DNA regulatory markers by quantitative PCR, whole blood, algorithm, including prostate-specific antigen, reported as likelihood of cancer.
0475U	Hereditary prostate cancer-related disorders, genomic sequence analysis panel using NGS, Sanger sequencing, MLPA, and array CGH, evaluation of 23 genes and duplications/deletions when indicated, pathologic mutations reported with a genetic risk score for prostate cancer.
0495U	Oncology (prostate), analysis of circulating plasma proteins (tPSA, fPSA, KLK2, PSP94, and GDF15), germline polygenic risk score (60 variants), clinical information (age, family history, prior negative biopsy), algorithm reported as risk of likelihood of detecting clinically significant prostate cancer.
0497U	Oncology (prostate), mRNA gene-expression profiling by real-time RT-PCR of 6 genes (FOXM1, MCM3, MTUS1, TTC21B, ALAS1, and PPP2CA), reported as a risk score for prostate cancer.
0534U	Oncology (prostate), microRNA/SNPs analysis by RT-PCR of 32 variants, using buccal swab, algorithm reported as a risk score.
0550U	Oncology (prostate), ELISA for total PSA and free PSA, serum, combined with age, reported as risk score. (TERMED 1/1/2026)
0572U	Oncology (prostate), ELISA for total PSA and free PSA combined with age, previous negative biopsy status, DRE findings, prostate volume, image/data reporting, algorithm reported as risk score for high-grade prostate cancer.
0591U	Oncology (prostate), high-throughput telomere length quantification by FISH, whole blood, diagnostic algorithm reported as risk of prostate cancer.
0609U	Oncology (prostate), immunoassay for total PSA and free PSA, serum or plasma, combined with clinical features, algorithm reported as a probability score for clinically significant prostate cancer.

1–10 of 18
1/2

Code updates / additionsCPT

CPT (unspecified)

CPT code added for PanGIA Prostate testing (exact code number not listed in referenced sections).

Periodic code set updatesmixed

code set updates (Q3/Q4 2023, Q1 2024, Q3 2024, 7/2024-10/2024)

Multiple periodic code set updates documented in revision history; specific codes not enumerated in cited chunks.

Covered CPT Codes (revisions noted)CPTCovered

PanGIA CPT (specific code not listed)

CPT code added for PanGIA Prostate testing (code not specified in cited revision notes).

Code changes and additions referencedCPT | mixed

PanGIA (CPT added)

CPT code added for PanGIA Prostate testing (specific CPT code number not listed in cited sections).

Code set updatesmixed

Multiple unspecified CPT/HCPCS

Numerous code set updates referenced across 2023-2025 in revision history; specific codes not present in cited chunks.

Added CPT codesCPT

PanGIA CPT (unspecified exact code)

CPT code added for PanGIA Prostate testing (exact CPT number not present in the cited extract).

Noted code additions in revision historyCPT

PanGIA CPT (unspecified)

CPT code added for PanGIA Prostate testing (policy history notes addition; exact code not provided in cited chunk).

Code set updates / Added codes (Q3 2025)mixed

Added code

Revision history notes a code was added in Q3 2025; the exact numeric code is not supplied in the cited chunks.

PSA ranges for test indications — ExoDx and PHI

ExoDx Prostate (IntelliScore) PSA rangeIntended for use in patients older than 50 years with no prior biopsy and PSA levels between 2–10 ng/mL.

Prostate Health Index (PHI) PSA rangeIndicated in the U.S. for men aged ≥50 years with PSA levels between 4–10 ng/mL.

Use with clinical factorsBoth tests are described as adjuncts to PSA and other clinical factors (age, race, family history) to inform biopsy decisions.

Germline polygenic risk score — variant count

Germline polygenic risk score variant countGermline polygenic risk score component includes 60 variants.

Test contextReported as part of a circulating plasma protein and risk-score algorithm (0495U) combined with clinical information.

Intended outputAlgorithm reported as likelihood of detecting clinically significant prostate cancer when combined with clinical variables.

Repeat testing criterion (policy addition)

Repeat testing criterion — policy changeA criterion for repeat testing was added to the policy (first referenced in the 7/2024 revision and noted in subsequent code-set updates).

Documentation requirementRevision history indicates documentation must support repeat testing when applicable (repeat testing criterion added 7/2024).

Operational impactRepeat-testing criterion appears in multiple updates and may affect prior authorization and claims adjudication.

Provider Actions: Authorization, Documentation, and Denial Risk

Prior Authorization
Prior authorization when clinical utility must be demonstrated
Prior authorization may be required when coverage is contingent on demonstration of clinical utility; include clinical rationale showing the test result is expected to change management.
Prior authorization tied to demonstration of clinical utility per evidence review and policy guidance.

Prior Authorization
Prior auth recommended for tests with insufficient clinical utility
Prior authorization is likely required for molecular/protein biomarker assays that lack demonstrated clinical utility; provide clinical justification and intended impact on biopsy or treatment decisions when requesting authorization.
Prior authorization for tests with insufficient clinical utility to avoid post-service denial.

Prior Authorization
Use guideline-aligned test codes on prior authorization requests
Use the specific U-/CPT codes listed for proprietary tests on prior authorization requests and claims so the plan can review medical necessity against guideline-aligned criteria.
Include one of the listed U-codes (e.g., 0133U, 0339U, 0343U, 0424U, 0475U, 0495U) when applicable.
Use guideline-aligned coding to permit medical necessity review.

Prior Authorization
Obtain prior authorization for unlisted codes
When ordering a test billed with an unlisted code, obtain prior authorization to avoid post-service denial; the policy states prior authorization is recommended for unlisted codes submitted for potentially covered services.
Prior authorization recommended for unlisted codes (e.g., 81479, 81599, 84999).

Prior Authorization
Check prior authorization after code/criteria updates
Prior authorization requirements may change after code or criteria updates (e.g., addition of PanGIA CPT, repeat‑testing criterion, and interim expansions); reference the updated policy when requesting authorization.
Prior authorization impacted by code and criteria updates including repeat‑testing and panel additions.

Prior Authorization
Confirm prior authorization using current codes and criteria
Confirm any prior authorization against the current policy revision and code set because revision history documents CPT additions and medical necessity updates that affect authorization rules.
Confirm authorization per the most recent revision history and code set updates.

Prior Authorization
Ensure prior auth aligns with current medical necessity criteria
Prior authorization, if required, will be governed by the policy's current medical necessity criteria; interim updates to medical necessity criteria through Q2 2025 are noted in the revision history.
Tie authorization requests to the updated medical necessity criteria documented in the policy.

Prior Authorization
Verify current CPT/U-codes for authorization requests
Verify the current CPT/U-codes before requesting prior authorization (policy history records multiple code set updates and addition of a PanGIA CPT code).
Verify newly added codes (e.g., PanGIA additions referenced) and any Q3/Q2 code set changes before submission.

Prior Authorization
Follow current policy codes and criteria for prior auth
Follow the current policy codes and criteria when requesting prior authorization; the policy history documents CPT additions and criterion expansions that govern authorization.
Prior authorization requirements should follow the current policy criteria and code list.

Prior Authorization
Follow the current code set for prior authorization
Use the policy's current code set when requesting prior authorization; multiple code set updates (including Q3 2025 additions) are recorded in the revision history and affect authorization decisions.
Follow the updated code list noted in recent code set updates when submitting authorization requests.

Note
(No additional action specified)
(Reserved)

Step Therapy
Step therapy not specified
No step therapy algorithms are specified in this policy for molecular prostate assays; do not assume step therapy requirements exist without plan/provider contract confirmation.
Step therapy not specified in the document.
Confirm with payer if any step requirements apply.

Step Therapy
Use standard clinical risk stratification before testing
Guidelines recommend selective — not routine — use of tissue‑based genomic biomarkers; consider standard clinical risk stratification (PSA, DRE, clinical factors) before ordering advanced assays.
Use standard risk stratification and guideline‑directed selection prior to ordering genomic/protein biomarker tests.

Note
(No additional action specified)
(Reserved)

Step Therapy
No explicit step therapy requirements stated
The policy includes no explicit step therapy requirements; follow guideline-recommended selective use and confirm any payer-specific step edits separately.
No explicit step therapy stated; verify with payer for any local utilization management rules.

Note
(No additional action specified)
(Reserved)

Documentation Required
Document clinical details (age, PSA, prior biopsy, DRE) when ordering tests
Document patient age, PSA level, prior biopsy history, DRE findings, and other clinical risk factors when ordering urine- or blood‑based prostate molecular assays because many tests are indicated for specific age/PSA ranges or prior biopsy status.
Include age, PSA, prior biopsy status, DRE findings, and relevant clinical risk factors on the prior authorization and medical record documentation.

Documentation Required
Document intended management impact of testing
Provide documentation that links testing to an actionable management decision (for example, how the result will influence biopsy, surveillance, or treatment) because clinical utility evidence is limited and reviewers may require demonstration of intended management impact.
Explain how the test result is expected to change management and provide follow-up plans or decision points.

Billing Rule
Use listed proprietary/CPT codes on claims and auth requests
Use the specific proprietary billing codes listed in the policy when available (e.g., 0133U, 0339U, 0343U, 0424U, 0475U, 0495U) to identify the test performed on claims and prior authorization requests.
Apply the listed U-codes or CPT codes for the named assays so the claim can be accurately reviewed.
Avoid generic/unlisted codes when a specific code is provided.

Prior Authorization
Prior authorization recommended when using unlisted codes
When submitting an unlisted code for a potentially covered service, obtain prior authorization to reduce risk of post‑service denial; the policy explicitly recommends authorization for unlisted codes to avoid denial.
Prior authorization recommended if using unlisted codes for potentially covered services.

Documentation Required
Reference policy revision history when submitting claims
Reference the policy's revision history and code updates when submitting claims or authorizations to ensure correct CPT/U-code selection and adherence to repeat‑testing criteria added in prior updates.
Cite the relevant policy revision or effective date if a code or criterion change affects the claim (e.g., PanGIA additions or repeat-testing rules).

Documentation Required
Reference policy effective version and revision entries
When submitting claims or prior authorization requests, reference the policy effective version and listed code‑set updates so reviewers can reconcile the request with the policy history and recent code additions.
Reference the policy effective date and the revision summary entry that added or modified the applicable code/criterion.

Documentation Required
Provide documentation supporting repeat testing requests
When repeat testing is requested, include documentation that supports the repeat‑testing criterion (a repeat testing criterion was added in 7/2024) and the clinical justification for re‑testing.
Document rationale and timing relative to prior test results to meet the repeat testing criterion.

Documentation Required
Reference policy revision history for coding/criteria questions
Reference the policy revision history when a code or clinical-criteria question arises; the history documents dates and nature of code set updates and interim criteria changes (including Q2 2025 interim updates).
Use the revision history to confirm applicable codes/criteria at the time of service.

Documentation Required
Note the policy effective version when submitting requests
Reference the policy effective version in authorization or claim submissions to ensure reviewers apply the correct codes and medical necessity criteria recorded for that effective date.
Include the policy effective date or revision note when relevant to the request.

Note

Denial Risk
Risk of denial when clinical utility is not demonstrated
Tests lacking demonstrated clinical utility may be denied; coverage decisions focus on clinical utility and the evidence review may trigger denials when clinical benefit is not shown.
Denial risk from insufficient clinical utility is explicitly noted in the evidence review and denial-risk section.

Denial Risk
Insufficient‑evidence tests are at denial risk
Tests with insufficient or inconclusive external evidence assessments (for example Hayes D2 or ECRI inconclusive ratings) carry a heightened risk of denial if clinical utility is not established.
Insufficient evidence (Hayes D2 / ECRI inconclusive) cited as grounds for potential denials.

Note

Denial Risk
Unlisted codes submitted for non‑covered services will be denied
The policy states unlisted codes submitted for non‑covered services will be denied as not covered; all unlisted codes are reviewed for medical necessity and correct coding at claim level.
Unlisted codes submitted for non‑covered services will be denied.
All unlisted codes are reviewed for medical necessity and pricing.

Denial Risk
Non‑covered panels (e.g., PanGIA) risk denial
Tests or panels listed as non‑covered (for example, PanGIA Prostate) may be denied; the revision history specifically added PanGIA to the list of non‑covered panels.
PanGIA Prostate is listed among non‑covered panels and may be denied if submitted.

Denial Risk
Denial risk from updated medical necessity criteria
Interim and Q2 2025 updates to medical necessity criteria may change coverage determinations; claims not meeting the updated criteria are at risk for denial.
Denial risk when requests do not meet updated medical necessity criteria from interim updates.

Note

Denial Risk
Risk of denial if outdated codes or criteria are used
Using outdated codes or prior criteria may result in claim denial; the policy documents multiple interim code set updates and criteria revisions that affect adjudication.
Risk from outdated codes/criteria if not using the current code set or criteria.

Documentation Required
Ensure coding and criteria are up to date
Verify that coding and medical necessity criteria are current before submitting claims or prior authorization requests; absence of up‑to‑date coding/criteria may adversely affect adjudication.
Coding/criteria currency is emphasized in the revision notes and affects adjudication.

Denial Risk
Potential denial risk when criteria change
Providers may face denials if requests do not meet updated medical necessity criteria; the revision history notes interim updates that changed coverage and may create potential denial risk.
Potential denial risk from criteria changes is documented in the revision history.

Background and Evidence Summary

Background: Multiple noninvasive and tissue-based molecular assays have been developed to improve detection of high-grade prostate cancer, reduce unnecessary biopsies, and to stratify risk for prognosis and treatment decisions. These tests measure diverse analytes (RNA, DNA methylation, proteins) in urine, blood (including exosomes or circulating tumor cells), or FFPE tissue and are intended to be used in conjunction with clinical factors such as PSA, age, DRE, family history, and prior biopsy status. Evidence quality across many assays is low, and guideline organizations recommend selective — not routine — use. (Background and evidence summaries: [[chunk 68]], [[chunk 38]], [[chunk 42]], [[chunk 45]], [[chunk 47]], [[chunk 49]], [[chunk 52]], [[chunk 53]], [[chunk 55]], [[chunk 59]])

Test Definitions and Key Terms

EpiScore — DNA methylation algorithm

DefinitionEpiScore is an algorithm that quantifies relative DNA methylation intensities of GSTP1, RASSF1, and APC from prostate biopsy tissue to compensate for biopsy under-sampling and improve risk stratification.

AnalytesMethylation intensities of three genes: GSTP1, RASSF1, and APC.

Intended useProposed to aid early detection of aggressive prostate cancer and improve risk stratification at diagnosis.

ExoDx Prostate (IntelliScore) — assay description and intended use

Test and methodExoDx Prostate (IntelliScore) is a urine exosome RNA assay measuring expression of PCA3, ERG, and SPDEF.

Intended populationDesigned for men >50 years with no prior biopsy and PSA 2–10 ng/mL to help predict absence of high-grade (Gleason ≥7) prostate cancer.

Role in careIntended to be used with PSA and clinical factors (age, race, family history) to inform initial biopsy decisions.

Progensa PCA3 — assay and indication

Test and sample typeProgensa PCA3 is a post-DRE urine-based assay measuring PCA3 noncoding RNA and generating a PCA3 score.

Indicated populationIndicated for men ≥50 years who have had one or more negative prostate biopsies and are being considered for repeat biopsy.

Intended useUsed with serum PSA and other risk indicators to estimate probability of a positive repeat biopsy and guide decisions to forego repeat biopsy in low-risk patients.

Clinical utility — definition

DefinitionClinical utility is evidence that use of the test leads to improved patient health outcomes (e.g., reduced morbidity or mortality) or meaningful changes in management demonstrated to benefit patients.

Evidence expectationsClinical utility evaluations should demonstrate that test results change management and improve measurable outcomes rather than only change decisions.

Policy relevanceCoverage decisions prioritize tests with demonstrated clinical utility; lack of utility can lead to denial (Hayes D2 or ECRI inconclusive findings cited).

Clinical validity — definition

DefinitionClinical validity is the ability of the test to accurately and reliably detect or predict the presence, absence, or risk of clinically relevant prostate cancer (e.g., aggressive disease).

ComponentsEvidence for clinical validity includes analytical validity (assay performance) and clinical studies showing correlation with disease presence or prognosis.

Limitations notedMany tests reviewed had very low-quality clinical validity evidence and lacked studies linking results to long-term outcomes.

Oncotype DX AR-V7 Nucleus Detect Test — definition

Test typeOncotype DX AR-V7 Nucleus Detect Test is a circulating tumor cell / AR-V7 protein assay evaluated to identify mCRPC patients unlikely to respond to AR-targeted therapies.

Evidence summarySystematic reviews found very low-quality evidence and inconclusive clinical utility; no peer-reviewed studies demonstrated improved patient outcomes when using the test.

Intended clinical roleProposed to inform treatment selection in metastatic castration-resistant prostate cancer but lacks demonstrated clinical utility per reviews.

Prolaris and ProMark — definitions

Prolaris — type and purposeProlaris is a tissue-based genomic prognostic test (cell-cycle progression score) intended to inform risk stratification and treatment decisions (e.g., active surveillance vs definitive therapy).

ProMark — type and purposeProMark is a tissue-based proteomic prognostic test intended to predict prostate cancer aggressiveness to aid management decisions.

Evidence limitationsSystematic reviews rated evidence as very low; clinical utility to demonstrate improved patient outcomes has not been established.

Hereditary prostate cancer-related genomic panel — description

Panel descriptionHereditary prostate cancer-related genomic panel (0475U) uses NGS, Sanger sequencing, MLPA, and array CGH to evaluate 23 genes and duplications/deletions when indicated.

ReportingPathologic mutations are reported with a genetic risk score for prostate cancer.

Intended contextUsed for hereditary prostate cancer evaluation when clinically indicated by family history or other risk features.

PanGIA Prostate — policy note and definition

Test namePanGIA Prostate (Genetic Institute of America) — panel referenced in the policy and added to revision history notes.

Coverage stancePanGIA Prostate was added to the list of non-covered panels per revision history (listed among non-covered panels).

Operational noteA CPT code for PanGIA Prostate testing was added in revision updates, though the specific CPT number is not detailed in the cited chunks.

Member Eligibility and Test Ordering Preconditions

No top-level eligibility requirement nodes are present in the provided excerpt. The document segments reviewed do not define explicit family history thresholds, prior-testing rules, or other formal eligibility conditions within these chunks; providers should consult the complete policy for any specific eligibility criteria that may apply.

No top-level eligibility requirement nodes are present in the provided excerpt. The excerpt does not include explicit prior-testing or sequencing requirements beyond general statements that many assays are intended to be used with prior PSA and clinical evaluation.

No top-level eligibility requirement nodes are present in the provided excerpt. The policy fragments do not specify distinct provider-type ordering restrictions or formal eligibility workflows in these chunks; consult the full policy for any such requirements.

Revision History and Policy Updates

2024-07-01code_addition

CPT code added for PanGIA Prostate testing (PanGIA CPT added during annual review).

2023-10code_set_update

Periodic code set updates recorded across multiple quarters (Q3/Q4 2023, Q1 2024 and Q3 2024 noted).

2025-07code_set_update

Q3 2025 code set update logged in revision history (noted as 'Q3 2025 code set update; Added code').

2024-07annual_review

Annual review (7/2024) with policy title change and addition of a CPT code; repeat testing criterion introduced during the 7/2024 annual review.

2024-08criteria_expansion

Interim update (8/2024) expanded coverage criteria to include additional NCCN-recommended tests; revision history also notes code additions and repeat testing criterion around this time.

2025-07code_addition

Q3 2025 code set update recorded with an added code in the revision history ('Q3 2025 code set update; Added code').

2024-07-01code_addition

PanGIA CPT code added (PanGIA Prostate testing referenced as having a CPT added during the 7/2024 annual review).

2024-07policy_change

Criterion for repeat testing introduced (first referenced/added in 7/2024) and recorded in subsequent interim updates affecting prior authorization and coding reviews.

2025-07code_set_updateLatest

Interim update to medical necessity criteria and code set updates noted in Q2 2025 and a Q3 2025 code set update; these revisions may impact prior authorization requirements.