CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Multimarker Serum Testing Related to Ovarian Cancer

Defines coverage for FDA-cleared multimarker serum tests (OVA1, Overa, ROMA) used as adjuncts in evaluating ovarian adnexal masses for malignancy for Commercial products; states these tests are not medically necessary for Commercial coverage and directs providers to member benefit booklets for determinations.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMultimarker Serum Testing Related to Ovarian Cancer

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 1, 2024

Next Review DateSep 20, 2024

Key ActionVerify member eligibility and benefits with the payer prior to ordering testing; prior authorization is not applicable but coverage is determined by the member's benefit booklet.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3FDA-cleared tests

Not medically necessaryCoverage stance (Commercial)

Commercial onlyPolicy applicability

81500,81503,0003UCodes referenced

Coverage Criteria

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Commercial — Not Medically Necessary

Covered when ALL of the following are met

Commercial coverage stance: All uses of OVA1, Overa and ROMA tests are considered not medically necessary for Commercial Products.

Includes preoperative evaluation of adnexal masses for malignancy/triage; selecting individuals for surgery; screening for ovarian cancer; evaluation of individuals with clinical or radiologic evidence of malignancy; postoperative testing and monitoring for recurrence; and evaluation of nonspecific signs or symptoms suggesting possible malignancy.

The policy identifies specific uses of OVA1, Overa, and ROMA that are considered not medically necessary for Commercial Products because the evidence is insufficient to demonstrate improved net health outcomes. Examples explicitly listed include: preoperative evaluation of adnexal masses for malignancy or triage; selecting individuals for surgery for an adnexal mass; screening for ovarian cancer; evaluation of individuals with clinical or radiologic evidence of malignancy; postoperative testing and monitoring to assess surgical outcome or detect recurrent disease; and evaluation of nonspecific signs or symptoms suggesting possible malignancy.

Some genetic testing and biomarker services may be excluded by contract or by state-mandated provisions. The policy directs providers to the Genetic Services Proprietary section of the Benefit Booklet (and related policies) to determine whether a given group’s plan has customized coverage, exclusions, or authorization requirements for biomarker testing referenced in the state mandate.

Coverage and payment for services described in this policy are governed by the member’s subscriber agreement, certificate, or employer agreement. Those documents control and may supersede the provisions of this medical policy for member-specific benefits and eligibility.

For Commercial Products, the policy states that all uses of the OVA1, Overa, and ROMA tests are considered not medically necessary. The rationale provided is that available evidence is insufficient to demonstrate an improvement in net health outcome, and therefore these tests are not covered for the commercial population described.

Coding and Regulatory References

ROMA CPT CodeCPT

81500

Oncology (ovarian) , biochemical assays of two proteins (CA-125 and HE4), utilizing serum, with menopausal status, algorithm reported as a risk score

OVA1 CPT CodeCPT

81503

Oncology (ovarian), biochemical assays of five proteins (CA-125, apolipoprotein A1, beta-2 microglobulin, transferrin, and pre-albumin), utilizing serum, algorithm reported as a risk score

Overa HCPCS CodeHCPCS

0003U

Oncology (ovarian) biochemical assays of five proteins (apolipoprotein A-1, CA 125 II, follicle stimulating hormone, human epididymis protein 4, transferrin), utilizing serum, algorithm reported as likelihood score

Regulatory Clearance Referencesmixed

510(k)

FDA 510(k) substantial equivalence determination referenced for OVA1 Test (K081754)

Provider Actions and Billing Notes

Prior Authorization

Prior Authorization Not Applicable

Prior authorization is not applicable for this policy. Providers should document that prior authorization is not required and consult the member's Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for any service-specific authorization rules.

If uncertain, verify member-specific benefits and any authorization requirements with the payer before providing services.

Note

Verify Coverage and Authorization

Benefits and coverage may vary by group and contract. Providers must verify eligibility and member-specific benefits prior to providing services and follow any authorization or coverage rules in the member’s plan documents.

Contact the provider call center for member-specific benefits and authorization requirements.
Confirm whether the member’s plan has customized benefit coverage or contract exclusions (for example, exclusions for certain genetic/biomarker testing).

Documentation Required

Benefit Verification and Member Financial Liability

Providers should refer to the member’s Benefit Booklet, Evidence of Coverage, or Subscriber Agreement to determine whether services are covered, medically necessary, or excluded under the member’s plan.

Non-covered or not medically necessary services may result in member financial liability — obtain written agreement from the member if charging them for non-covered services.
For self-funded groups with exclusions (e.g., biomarker/genetic testing), confirm applicable contractual exclusions before billing.

Denial Risk

Denial Risk for Commercial Coverage

All uses of the OVA1, Overa, and ROMA tests for Commercial products are considered not medically necessary and are subject to denial when billed under Commercial coverage.

Not medically necessary uses include, but are not limited to: preoperative evaluation of adnexal masses, selecting individuals for surgery, screening for ovarian cancer, evaluation with clinical or radiologic evidence of malignancy, postoperative monitoring for recurrence, and evaluation of nonspecific signs or symptoms suggesting possible malignancy.

Billing Rule

Member Financial Liability Note

If a service is determined to be not medically necessary or not a covered benefit under the member’s plan, the member may be financially responsible for the service. Providers must follow participation agreement provisions regarding billing members for such services.

Obtain the member’s written agreement prior to providing services expected to be non-covered or not medically necessary if you intend to bill the member.
Refer to the provider participation agreement for applicable billing and collection provisions.

Definitions

Epithelial ovarian cancer — collective term definition

TermEpithelial ovarian cancer

IncludesHigh-grade serous epithelial ovarian, fallopian tubal, and peritoneal carcinomas

Rationale for groupingGrouped due to shared pathogenesis, clinical presentation, and treatment

Clinical noteSurgery is required for definitive diagnosis; most adnexal masses are benign (≈68%)

ROMA — Risk of Ovarian Malignancy Algorithm definition (CPT 81500)

NameRisk of Ovarian Malignancy Algorithm (ROMA)

DescriptionA serum‑based algorithm using CA‑125 and HE4 with menopausal status; reported as a risk score

CPT code81500 — Oncology (ovarian), biochemical assays of two proteins (CA‑125 and HE4), algorithm reported as a risk score

Intended useAid, in conjunction with clinical assessment, to assess likelihood of malignancy in women with adnexal masses

OVA1 / Overa — multimarker panels definition (CPT 81503; HCPCS 0003U)

TestsOVA1 and Overa (next‑generation OVA1)

DescriptionMultimarker panels combining multiple protein assays to generate a risk/likelihood score for malignancy in adnexal masses

CPT/HCPCS codes81503 — OVA1 (five‑protein panel); 0003U — Overa (five‑protein panel, next generation)

Protein components (examples)OVA1: CA‑125, apolipoprotein A1, beta‑2 microglobulin, transferrin, pre‑albumin; Overa: apolipoprotein A‑1, CA‑125 II, FSH, HE4, transferrin

OVA1 / multivariate index assays — FDA-reviewed multimarker proteomic assays definition

DefinitionFDA‑reviewed multimarker proteomic and multivariate index assays (e.g., OVA1) designed to assess likelihood of ovarian malignancy in women with adnexal masses

Regulatory pathwayCleared through FDA 510(k) process (OVA1 and ROMA referenced; Overa cleared as next‑generation OVA1)

Intended roleAdjunct to clinical and radiologic assessment to triage patients for referral to gynecologic oncology

LimitationsNot intended as standalone screening or diagnostic tests; developed and evaluated only in patients with adnexal masses and planned surgery

ROMA / HE4 / CA125 — biomarkers and algorithms used to stratify malignancy risk preoperatively

Biomarkers includedHE4 and CA‑125 frequently used in combination

Algorithm exampleROMA uses CA‑125 and HE4 plus menopausal status to produce a risk score

Clinical useUsed to stratify preoperative malignancy risk in women presenting with adnexal masses as an adjunct to clinical assessment

Evidence considerationsMultiple studies and meta‑analyses have evaluated HE4, CA‑125, and ROMA; performance varies by menopausal status and population

OpenPayer

Multimarker Serum Testing Related to Ovarian Cancer

Coverage Criteria

Coding and Regulatory References

Provider Actions and Billing Notes

Background

Definitions