Provide referenced procedure/CPT/PLA/U codes when requesting authorization

Procedure (CPT/PLA) and miscellaneous U-codes are listed in the policy for reference; providers should supply these codes when requesting prior authorization but confirm coverage and prior authorization applicability with the member-specific benefit plan document.

• Examples of PLA/CPT codes listed for reference: 0011M, 0012M, 0013M, 0016M, 0020M, 0005U, 0018U, 0019U, 0026U, 0036U, 0045U
• Examples of genomic panel CPT codes listed: 81457, 81458, 81459, 81462, 81463, 81464, 81479, 81504, 81518, 81519, 81521, 81524, 81529, 81540, 81546, 81551, 81552, 81599

Confirm prior authorization per member benefit plan

The policy states that prior authorization requirements are determined by the member-specific benefit plan and applicable laws; providers must check the member's plan to know whether prior authorization is required for a requested molecular oncology test.

• Listing of a code in this policy does not imply the service is covered; benefit coverage and prior authorization depend on the member-specific benefit plan document.

Reference applicable CPT/PLA/unlisted codes in authorization/billing

Use the policy's enumerated CPT/PLA/unlisted codes when completing prior authorization or billing submissions for molecular oncology testing; these codes are provided for reference in the policy's coding section.

• Provider should reference specific PLA codes (e.g., 0011M, 0016M, 0026U, 0244U) or CPT panel codes (e.g., 81457–81464, 81479) as applicable when requesting authorization or submitting claims.

No payer-level prior authorization specified in these excerpts — check plan

The excerpts do not specify payer-level universal prior authorization mandates; absence of explicit PA rules in these sections means providers must rely on member plan documents to determine any PA requirement.

• Policy clinical-study text and evidence sections do not define a payer-wide prior authorization requirement in the provided excerpts.

Order tests only in guideline-indicated clinical contexts

Order multigene assays in clinical scenarios aligned with guideline recommendations (ASCO, NCCN, NICE) — for example, GEPs (Oncotype DX, MammaPrint, Prosigna, EndoPredict, BCI) in ER+/HER2- early breast cancer when node/menopausal criteria match guideline-specified groups.

• ASCO supports Oncotype DX, MammaPrint, BCI, EndoPredict to guide adjuvant decisions in postmenopausal or >50 y with node-negative or 1–3 node disease.
• NCCN prefers the 21-gene Oncotype DX for certain pN0/pN1 settings and notes GEAs are not required for staging.

Document clinical rationale for broad-panel or ctDNA testing

When requesting broad NGS panels or plasma ctDNA (liquid biopsy), document the clinical rationale in the request — typical reasons include advanced/metastatic disease, unavailable or unsafe tissue biopsy, or need to assess eligibility for targeted therapy or clinical trials.

• ASCO and NCCN recommend tissue-based NGS when feasible and allow ctDNA when tissue is unavailable or the patient is unfit for biopsy.
• Document that testing is intended to identify actionable driver alterations or to guide clinical trial enrollment.

Ensure test indication matches studied clinical scenarios

Match the intended test use to the clinical scenarios studied in the evidence base; for example, document that prostate genomic classifier use is for post-prostatectomy adverse pathology or that Decipher-informed radiation decisions mirror trial contexts.

• For post-RP adjuvant decisions, document adverse pathology (pT3/4, positive margins) and undetectable PSA when using Decipher.
• For radiation dose escalation decisions, document that the clinical scenario aligns with the trial-derived contexts where the signature was evaluated.

Order somatic NGS in metastatic prostate cancer when it will affect therapy

For metastatic prostate cancer patients being considered for biomarker-directed systemic therapy, order somatic tumor NGS (archival tissue preferred; ctDNA acceptable if biopsy not feasible) and document that results may change treatment or trial eligibility.

• ASCO recommends somatic NGS for metastatic PCa when biomarker-directed treatment is being considered; archival tissue preferred for initial testing.
• If ctDNA is used, document inability to obtain tissue and be aware ctDNA collection is not recommended when PSA is undetectable.

Provide justification that test results will affect management

Only request molecular biomarkers selectively when the test result is expected to influence management; prior authorization reviewers may require documentation that the result will change care.

• ASCO and NCCN advise offering tests (e.g., Decipher, GPS, Prolaris) when results are likely to change decisions (active surveillance, adjuvant RT, systemic therapy).
• Routine ordering of biomarkers without a management-impact justification is not recommended.

No universal prior authorization requirement stated here — verify plan rules

The excerpts do not define a single prior authorization rule; providers must check member-specific rules for PA applicability for molecular oncology tests.

• Policy clinical/evidence sections summarize guideline contexts but do not impose a universal payer PA requirement in the provided excerpts.

Document clinical stage and rationale for DecisionDx‑UM or uveal melanoma GEP

When ordering DecisionDx-UM or similar uveal melanoma GEP tests to guide surveillance intensity or adjuvant trial stratification, include documentation of tumor stage, PRAME status (if available), and the clinical rationale to support coverage review.

• DecisionDx-UM is considered medically necessary for primary localized uveal melanoma when no metastatic disease is present and the individual has not previously had DecisionDx-UM for the current diagnosis.
• Harbour et al. demonstrate DecisionDx-UM and PRAME improve metastatic risk stratification and can inform surveillance/trial stratification; document intended management changes.

Anticipate prior authorization for broad genomic profiling; include stage and intent

Expect prior authorization to be likely for broad genomic profiling in settings where guidelines recommend larger NGS panels (e.g., advanced-stage disease or to inform trial enrollment); include clinical-stage and treatment-intent documentation to support authorization.

• NCCN and ASCO recommend broader genomic profiling (often >50 genes) in stage III–IV or recurrent disease when results might guide therapy or trial eligibility.
• CUPISCO used CGP with a molecular tumor board to select molecularly guided therapy; prior authorization may request CGP results and tumor board recommendations.

Provide CGP results and MTB documentation for CUP molecularly guided therapy requests

When CGP is used to guide therapy in cancers of unknown primary (CUP), include comprehensive genomic profiling results and, if available, molecular tumor board recommendations to support requests for coverage of molecularly guided therapy.

• CUPISCO randomized participants to molecularly guided therapy based on CGP and MTB selection; for authorization, document tissue availability, CGP findings, and MTB rationale where applicable.
• NCCN lists tumor/tissue and cfDNA NGS as an option in the occult primary workup (category 2A).

Cite guideline (NCCN) category when requesting NGS/cfDNA for occult primary

Note guideline recommendation status (e.g., NCCN category 2A) in prior authorization requests for NGS or cfDNA testing in occult primary/CUP workups to demonstrate alignment with practice guidelines.

• NCCN recommends biomarker testing on tumor tissue and/or cfDNA as an option in the workup of suspected metastatic malignancy with occult primary (category 2A).
• CUPISCO provides randomized evidence of PFS benefit with molecularly guided therapy in selected patients.

Limit to one predictive GEP per breast tumor (BCI exception for EET)

Do not order more than one predictive GEP for the same breast tumor — the policy states only one predictive GEP per tumor is medically necessary; document if BCI is requested for extended endocrine therapy even after a prior GEP.

• Policy: "The use of more than one predictive GEP for the same tumor in an individual with breast cancer is unproven and not medically necessary."
• Exception: Breast Cancer Index may be used once to evaluate extended endocrine therapy even if another GEP was previously performed.

Verify preventive-benefit routing for cancer-screening molecular tests

Benefit-routing note: cancer screening tests that may be preventive are governed by the plan's Preventive Care Services policy; check benefit routing before submitting authorization for screening-related molecular tests.

• The policy refers screenings eligible under preventive care to the separate Preventive Care Services policy.

No step-therapy mandates here; follow guideline-preferred assay sequencing and document deviations

No step-therapy sequencing mandates are described in these excerpts; providers should follow guideline-preferred assay sequencing (e.g., NCCN/ASCO preferences) and include clinical justification when requesting non-preferred assays.

• Policy excerpts state no explicit step therapy requirements in the provided segments.
• ASCO/NCCN indicate preferred assays for certain scenarios (e.g., Oncotype DX for 21-gene use); document reason if ordering an alternative assay.

Document intended management impact when ordering prostate genomic classifiers

When using prostate genomic tests (Decipher, GPS, Prolaris) document that the test result is expected to alter management (e.g., support active surveillance selection or inform adjuvant vs salvage radiation decisions); routine ordering without management-impact justification is discouraged.

• ASCO recommends offering these assays when results are likely to affect management and cautions against routine ordering.
• Decipher may inform postprostatectomy adjuvant vs early salvage RT when adverse pathology and undetectable PSA are present; document these clinical features.

Provide adverse pathology and PSA status when using Decipher to guide post‑RP radiation decisions

Decipher results used to inform adjuvant versus early salvage radiation after prostatectomy should be accompanied by documentation of adverse pathology and undetectable PSA to mirror studied contexts.

• NRG/RTOG and prospective/ancillary analyses used Decipher in post-RP contexts with adverse pathology; document pathologic details and PSA status when requesting coverage for related management changes.

Document tumor size/stage in addition to GEP class before changing surveillance/management

Before escalating surveillance or interventions based on GEP in melanoma or uveal melanoma, document tumor size/stage alongside GEP class because tumor size remains an important predictor and should be considered in conjunction with molecular results.

• Miguez et al. found tumor size provided additional prognostic value independent of GEP class in uveal melanoma; DecisionDx-UM results should be integrated with tumor size/stage.
• 31-GEP influenced SLNB decisions in DECIDE, but tumor location/size were important confounders; document these when ordering.

Include Decipher Bladder subtype when using assay to support neoadjuvant chemotherapy decisions

Decipher Bladder/urothelial genomic classifier results used to justify neoadjuvant chemotherapy should include molecular subtype documentation (nonluminal vs luminal) because evidence of benefit was subtype-dependent in retrospective cohorts.

• Reike et al. reported nonluminal subtypes derived significant OS benefit from NCT compared with luminal subtypes; include subtype and clinical staging when requesting authorization for NCT based on GC.

For CUP molecular therapy requests, provide CGP results and MTB recommendation as in CUPISCO

In CUP contexts where molecularly guided therapy is proposed, note that the CUPISCO trial assigned therapy after CGP and molecular tumor board review; providers should document tissue availability, CGP actionable results, and any MTB recommendation to support coverage.

• CUPISCO required available tissue for CGP and used an MTB to select MGT arms; PFS benefit was shown overall and more so when actionable alterations were identified.

Provide required clinical and specimen documentation to support test medical necessity

Document specific clinical indications, specimen type and quality (e.g., FFPE block passing QC, CNB vs surgical specimen), and pre/post-test counseling or decision impact when ordering tests where evidence and guidelines tie utility to those elements (e.g., Prosigna, MammaPrint/BluePrint, ExoDx, DecisionDx-UM).

• Prosigna analysis: report QC pass (e.g., 1,478 of 1,620 blocks passed) to support specimen adequacy.
• MammaPrint/BluePrint concordance supports CNB use; document specimen source.
• For ExoDx, document PSA (commonly 2–10 ng/mL), age, indication (initial vs repeat biopsy), and MRI status.
• For DecisionDx-UM, document that biopsy was performed (if applicable), tumor stage, and that results will inform surveillance or trial eligibility.

Risk of denial if ordering assays listed as unproven/not medically necessary

Tests designated as unproven or not medically necessary in the policy (an extensive list) may be denied if requested for those indications; providers should avoid ordering listed unproven assays for diagnostic/management decisions without plan approval.

• Policy: "All other molecular oncology testing for solid tumor cancer is unproven and not medically necessary…" with explicit example lists (e.g., CancerTYPE ID, many multicancer detection tests, and named bladder and melanoma tests).
• Ordering an assay listed in the Unproven/Not Medically Necessary section risks denial when used for those indications.

Code listing does not equal coverage — confirm with plan document

Listing a code in the policy is informational only; inclusion does not imply the service is covered or guarantee reimbursement — providers must verify coverage with the member's benefit plan.

• Policy explicitly states listing of a code does not imply coverage; benefit coverage is determined by the member-specific plan and applicable law.

No explicit procedural authorization/denial triggers stated here — provide clinical justification

The policy does not specify explicit provider action triggers (e.g., automatic denials) in the cited chunks; authorization and denial decisions are based on documented medical necessity, guideline alignment, and member benefits.

• Excerpts list codes and evidence but provide no explicit procedural authorization or denial trigger language in the provided text.

Other breast/DCIS GEP assays have limited evidence — risk of noncoverage

Genomic expression profile assays for breast cancer or DCIS not specifically covered by the policy (e.g., DCISionRT, Oncotype DX Breast DCIS Score) are identified as having limited evidence and may be subject to noncoverage or denial; avoid ordering them for routine clinical use without prior approval.

• Policy lists several breast DCIS and other GEP assays as unproven/not medically necessary; NICE and Hayes reviews cite limited evidence for some uses.

Do not use ctDNA in place of tissue diagnosis without justification

Do not substitute ctDNA for tissue diagnosis when tissue is available; ctDNA is intended for advanced/metastatic settings or when tissue biopsy is unsafe or unfeasible and may be denied if used in lieu of tissue without justification.

• NCCN and ASCO guidance: tissue testing should be attempted when feasible; ctDNA testing should not replace tissue diagnosis and is generally for advanced/metastatic settings or when biopsy is not possible.

Evidence insufficiency for certain assays may trigger denial — document guideline-aligned rationale

Evidence insufficiency for some prostate genomic assays (e.g., GPS, Prolaris) and other tests may lead to noncoverage or denial for indications lacking robust outcome data; include supporting clinical rationale and cite guideline-endorsed uses to mitigate denial risk.

• Hayes assessments found insufficient/low-quality evidence for some GPS and Prolaris uses (e.g., informing treatment intensity in unfavorable intermediate/high-risk PCa).
• Providers should document that test results will change management and align with guideline-recommended contexts.

Avoid ctDNA collection when PSA is undetectable (document if exception)

Plasma ctDNA testing is not recommended when PSA is undetectable for prostate cancer evaluation; do not submit ctDNA collection claims for such patients without documented clinical justification.

• NCCN: collection of plasma ctDNA is not recommended when PSA is undetectable.

Risk of denial for tests with low/insufficient evidence (e.g., MyPath, PLA)

Tests with insufficient or low-quality evidence (e.g., MyPath Melanoma, some PLAs) may be denied; providers should avoid relying solely on such assays for definitive management decisions and include corroborating clinical/pathologic evidence if seeking coverage.

• Hayes concluded MyPath Melanoma evidence is low/very low quality; DECIDE and other melanoma studies show variable quality—use adjunctively and document other supporting data.

Do not substitute predictive GEP for guideline-recommended staging/SLN discussion

Predictive GEP testing should not be used to replace standard staging or sentinel lymph node (SLN) surgical discussion; requests that propose GEP as a substitute for guideline-recommended staging may be denied unless included in a clinical study context.

• NCCN: predictive GEP testing to replace surgical oncology discussion of pathological staging/SLN is not recommended outside clinical trials.
• DECIDE shows 31-GEP influenced SLNB decisions, but guidelines caution against using GEP as a replacement for standard staging.