CurrentCapital BluecrossPolicy MP 2.270

Multimarker serum testing related to ovarian cancer (OVA1, Overa, ROMA, OvaWatch)

This medical policy governs coverage of multimarker serum-based tests (OVA1, Overa, ROMA, OvaWatch and related MAAA tests) for evaluation of ovarian adnexal masses and other proposed indications, specifying that all uses are investigational and therefore not covered.

Policy Summary

PayerCapital Bluecross

PolicyMultimarker serum testing related to ovarian cancer (OVA1, Overa, ROMA, OvaWatch)

Policy CodePolicy MP 2.270

Change TypeAdministrative updates (coding/background), clarified OvaWatch status

Effective Date11/01/2025

Next Review Date

Key ActionClaims for OVA1, Overa, ROMA, OvaWatch and related multianalyte assays for the listed uses should be considered investigational and are not covered; procedure codes 81500 and 81503 are listed as investigational and not covered.

POLICY UPDATE CHANGES

Added OvaWatch to statement (04/10/2023) and noted it is not FDA approved (per background).

Removed NCCN statement (11/19/2024).

Removed procedure codes 0003U and 0375U (08/13/2025).

New code 0507U added effective 10/01/2024 then moved to MP 2.277 (02/26/2025).

Multiple administrative and consensus reviews with no change to clinical policy statement (2019-2025).

1Coverage Position

3FDA-cleared tests referenced

1Tests mentioned without FDA approval

Coverage Summary

This policy governs coverage of multimarker serum-based tests (OVA1, Overa, ROMA, OvaWatch and related MAAA tests) for evaluation of ovarian adnexal masses and other proposed indications. All uses are considered investigational and therefore not covered.

Overview: All uses of multimarker serum tests (including OVA1, Overa, ROMA, OvaWatch and related multianalyte assays with algorithmic analyses) are considered investigational/not covered, including preoperative risk assessment, screening, selection for surgery, evaluation of suspected malignancy, evaluation of nonspecific signs or symptoms, and postoperative monitoring. Policy effective date: 11/1/2025. Last review date: 02/26/2025.

Policy metadata

Policy NumberMP 2.270

SubjectMultimarker serum testing related to ovarian cancer (OVA1, Overa, ROMA, OvaWatch)

Coverage PositionInvestigational — not covered for all uses

Effective Date11/1/2025

Last Review02/26/2025

Medical Necessity / Investigational Criteria

Multimarker serum tests — investigational uses and intended use context

All uses of the OVA1, Overa, OvaWatch, and ROMA tests are investigational, including but not limited to:

Investigational / Not Covered Uses

Preoperative evaluation of adnexal masses to triage for malignancy
Screening for ovarian cancer
Selecting individuals for surgery for an adnexal mass
Evaluation of individuals with clinical or radiologic evidence of malignancy

Coding

Investigational; therefore, not covered Procedure CodesCPTNot Covered

81500
81503

Administrative coding updates for operational awareness: OvaWatch was added to the policy statement (04/10/2023) and later administrative updates show codes were added and moved—new code 0507U was added effective 10/01/2024 then moved (02/26/2025), and procedure codes 0003U and 0375U were removed (08/13/2025). The policy continues to consider all listed tests investigational.

Provider Actions / Billing Impact

Denial Risk

Claims for multimarker ovarian tests are not covered

Claims for OVA1, Overa, ROMA, OvaWatch and related multianalyte assays for the listed uses should be considered investigational and are not covered; procedure codes 81500 and 81503 are listed as investigational and not covered.

81500
81503

Background, Evidence, and Definitions

Background: Multimarker serum tests (MAAAs) were developed to aid assessment of adnexal masses. Three tests have been FDA-cleared for marketing: OVA1 (cleared 2009), ROMA (cleared 2011), and Overa (cleared 2016). OvaWatch was introduced in December 2022 but was not FDA approved at the time of this policy.

Evidence and guidance: Studies show these tests have moderate to high sensitivity with variable specificity (examples: OVA1 sensitivity 92% specificity 42%; Overa sensitivity 94% specificity 65%; ROMA sensitivity 90% specificity 67%). However, no randomized trials demonstrate that management guided by these tests improves health outcomes. National guidance notes that patients with suspected ovarian cancer should be evaluated by an experienced gynecologic oncologist, and multimarker tests are intended to be used in conjunction with clinical assessment rather than as stand-alone tests.

Evidence	Key point
OVA1 diagnostic performance	Sensitivity 92%, specificity 42% when used with clinical assessment
Overa diagnostic performance	Sensitivity 94%, specificity 65% when used with clinical assessment
ROMA diagnostic performance	Study reported sensitivity 90%, specificity 67% when used with clinical assessment
Net health outcome	Insufficient evidence; no trials showing improved outcomes when referral based on these tests

Definitions

MAAAMultianalyte assays with algorithmic analyses — combinations of several lab tests plus a proprietary algorithm to produce a risk score.

Revision History

04/10/2023clarified

Added OvaWatch to statement and noted it is not FDA approved.

11/19/2024removed

Administrative change: Removed NCCN statement from background.

10/01/2024added

New code 0507U added (effective 10/01/2024); later moved between policies.

Policy Summary

PayerCapital Bluecross

PolicyMultimarker serum testing related to ovarian cancer (OVA1, Overa, ROMA, OvaWatch)

Policy CodePolicy MP 2.270

Change TypeAdministrative updates (coding/background), clarified OvaWatch status

Effective Date11/01/2025

Next Review Date

On This Page

Evaluation of individuals with nonspecific signs or symptoms suggesting possible malignancy

Postoperative testing and monitoring to assess surgical outcome and/or to detect recurrent malignant disease following treatment

Intended/cleared use context (informational)

OVA1 and Overa intended for patients with adnexal masses when clinical assessment does not clearly indicate cancer; intended to further assess likelihood of malignancy
ROMA intended as an aid, in conjunction with clinical assessment, to assess whether a premenopausal or postmenopausal woman with an adnexal mass is at high or low likelihood of finding malignancy on surgery
OvaWatch intended for assessing risk of ovarian cancer for women with adnexal masses considered indeterminate or benign in initial clinical assessment (not FDA approved as of policy)

Test thresholds

OVA1 score (premenopausal)<5.0: low; ≥5.0: high

OVA1 score (postmenopausal)<4.4: low; ≥4.4: high

Overa score (premenopausal)<5.0: low; ≥5.0: high

Overa score (postmenopausal)<5.0: low; ≥5.0: high

ROMA threshold (premenopausal)≥1.3: high

ROMA threshold (postmenopausal)≥2.77: high

02/26/2025administrative

Code 0507U moved to MP 2.277 per consensus review.

08/13/2025removed

Administrative coding update: Removed procedure codes 0003U and 0375U.

2019-2025administrativeLatest

Multiple administrative and consensus reviews with no change to the clinical policy statement.