CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Multimarker Serum Testing Related to Ovarian Cancer (OVA1, Overa, ROMA)

Coverage determination for commercial Blue Cross Blue Shield - Rhode Island products regarding FDA-cleared multimarker serum tests (OVA1, Overa, ROMA) used in assessment of ovarian adnexal masses; describes intended uses, regulatory status, and payer coverage stance.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMultimarker Serum Testing Related to Ovarian Cancer (OVA1, Overa, ROMA)

Policy CodePolicy N/A

Change TypeNo material change

Effective DateOct 1, 2015

Next Review DateN/A

Key ActionDo not order OVA1, Overa, or ROMA for commercial members because all uses are considered not medically necessary and may be denied.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3FDA-cleared tests

68%Estimated benign rate

42-67%Specificity range

92-94%Sensitivity range

3Biomarkers cited

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Coverage Determination

Not Medically Necessary

Covered when ALL of the following are met:

Policy statement: All uses of the OVA1, Overa, and ROMA multimarker serum tests for commercial products are considered not medically necessary unless direct evidence of clinical usefulness is demonstrated.

From policy summary; applies to commercial products

Examples of not medically necessary indications: Preoperative evaluation of adnexal masses to assess for malignancy or to triage; selecting individuals for surgery for an adnexal mass; screening for ovarian cancer; evaluation of individuals with clinical or radiologic evidence of malignancy; postoperative monitoring to assess surgical outcome and/or detect recurrent malignant disease; evaluation of individuals with nonspecific signs or symptoms suggesting possible malignancy.

Enumerated examples from policy

Evidence requirement: No direct randomized trial evidence demonstrates that referral or management based on these FDA‑cleared multimarker serum tests improves health outcomes; evidence is insufficient to show improvement in net health outcome.

Policy requires direct evidence of clinical usefulness (preferably randomized trials)

The tests are not intended for use in women without adnexal pelvic masses (i.e., for ovarian cancer screening). The FDA requires manufacturers to include a Black Box Warning because off‑label screening use carries public health risks from false‑positive and false‑negative results, including morbidity and mortality associated with unnecessary surgery or missed malignancy. Use of these assays outside their intended population (for example, general population screening) is therefore contraindicated by the device labeling and poses known safety risks.

This policy does not substitute for member‑specific coverage determinations. Benefits and eligibility are governed by the member's subscriber agreement and employer agreement, which supersede this medical policy. Providers with questions about a member's covered benefits should contact the provider call center to verify eligibility and benefits before ordering testing.

For commercial Blue Cross Blue Shield products, all uses of OVA1, Overa, and ROMA tests are considered not medically necessary. This includes, but is not limited to: preoperative evaluation or triage of adnexal masses to assess malignancy risk; selecting patients for surgery for an adnexal mass; screening for ovarian cancer; evaluation of individuals with clinical or radiologic evidence of malignancy; postoperative monitoring for recurrence; and evaluation of patients with nonspecific signs or symptoms suggesting possible malignancy. The available evidence is insufficient to show these tests improve net health outcomes in these contexts.

When services are determined to be not medically necessary under this policy, providers should be aware of billing and member liability implications. Services deemed not medically necessary may not be billed to the member unless the provider has obtained a prior written agreement with the member to accept financial responsibility. Providers should consult their participation agreements and confirm any required documentation before proceeding.

Coding and Billing

Covered CPT Codes (listed commercially but policy position is NMN)CPTNot Covered

81500

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

Not medically necessaryCPTNot Covered

81503

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

Not medically necessary (PLA/Proprietary code)PLANot Covered

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 A1, - likelihood score

Provider Requirements & Actions

Prior Authorization

Prior Authorization / Code-level Requirement

Not applicable

Prior Authorization

The excerpt does not state specific prior authorization requirements for biomarker or algorithm testing.

Denial Risk

All uses of OVA1, Overa, and ROMA for Commercial Products

All uses of OVA1, Overa, and ROMA for commercial products are considered not medically necessary and may be denied.

All indications (preoperative evaluation, selecting individuals for surgery, screening, evaluation with clinical or radiologic evidence of malignancy, postoperative monitoring, evaluation of nonspecific signs/symptoms) are considered not medically necessary

Clinical Background

Epithelial ovarian cancer is a collective term that includes high‑grade serous ovarian carcinoma as well as fallopian tube and peritoneal carcinomas. Most adnexal masses are benign (approximately 68% in some estimates), and management decisions should be guided by clinical assessment and radiologic evaluation. Serum multimarker assays (OVA1/Overa/ROMA) were developed as adjunctive tools to estimate likelihood of malignancy for adnexal masses, but they are not intended as stand‑alone diagnostics or screening tests; surgical staging and referral to a gynecologic oncologist remain the standard for masses with a high likelihood of malignancy.

Definitions and Intended Use

Epithelial ovarian cancer — definition and key points

DefinitionCollective term for high-grade serous epithelial ovarian, fallopian tubal, and peritoneal carcinomas with shared pathogenesis, clinical presentation, and treatment

Clinical implicationSurgery is the only way to diagnose ovarian cancer; masses with high likelihood of malignancy should undergo surgical staging by a gynecologic oncologist

EpidemiologyEstimated 19,880 U.S. diagnoses in 2021 with ~12,810 deaths; adult women with an adnexal mass have ~68% likelihood of a benign lesion

Diagnostic limitationNo serum biomarker currently distinguishes between these carcinoma types

Intended use and regulatory status (OVA1 / Overa / ROMA)

Intended use (summary)Adjunctive aid to assess likelihood of malignancy in women presenting with adnexal/adnexal masses; to be used in conjunction with clinical assessment and radiologic evaluation

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMultimarker Serum Testing Related to Ovarian Cancer (OVA1, Overa, ROMA)

Policy CodePolicy N/A

Change TypeNo material change

Effective DateOct 1, 2015

Next Review DateN/A

Key ActionDo not order OVA1, Overa, or ROMA for commercial members because all uses are considered not medically necessary and may be denied.

SourceLink

On This Page

Documentation Required

FDA Black Box Warning: Off-label Risks

The FDA has issued a black box warning to highlight risks of off-label use of ovarian adnexal mass assessment score test systems. Manufacturers must warn against use for screening asymptomatic women, use as a stand-alone diagnostic, or use to determine need for surgery because such uses can lead to harm from false-positive or false-negative results and inappropriate management.

Not intended for screening women without adnexal pelvic masses
Not intended as a stand-alone diagnostic test
Not intended to be used alone to decide whether to proceed with surgery

Note

Member Financial Liability Risk

Services determined not to be medically necessary (or medically necessary services that are non-covered benefits) may result in member financial liability. Providers should verify member-specific benefits and eligibility and inform members in writing if they will be financially responsible prior to providing non-covered services as required by participation agreements.

For member-specific benefits or eligibility questions providers should call the provider call center
Providers may not bill members for non-covered services unless the member is informed and has agreed in writing in advance

Documentation Required

Tests Intended to be Used in Conjunction with Clinical and Radiologic Assessment

These multimarker tests are intended to be used only in conjunction with clinical assessment and radiologic evaluation (eg, pelvic exam, CA-125, ultrasound) and are not intended to be used as stand-alone tests.

Documentation should include clinical assessment and radiologic findings when these tests are considered

Note

Clinical Guidance (ACOG/NCCN) — Referral to Gynecologic Oncologist

Clinical guidance (ACOG) recommends referral to a gynecologic oncologist based on clinical factors (including CA-125 levels and ultrasound findings). For premenopausal and postmenopausal women, thresholds and additional clinical features (eg, ascites, nodular or fixed mass, evidence of metastasis) inform referral decisions. Multimarker tests are described as potential alternatives to CA-125 for referral decisions but are not substitutes for clinical judgment.

ACOG 2016 bulletin: use separate criteria for premenopausal and postmenopausal women; CA-125 threshold for postmenopausal women is lower (35 U/mL)
Very elevated CA-125 with other clinical factors may prompt referral to gynecologic oncology

Tests referencedOVA1 (Aspira Labs), ROMA (Fujirebio Diagnostics), Overa (next-generation OVA1)

Regulatory statusOVA1 cleared by FDA 510(k) July 2009; ROMA cleared September 2011; Overa cleared March 2016

Limitations / warningsFDA black box warning: not for screening women without adnexal pelvic masses, not as stand-alone diagnostic, and not to determine need for surgery due to risks of false positives/negatives and off-label use