CurrentOscar HealthPolicy N/A

In Vitro Chemoresistance and Chemosensitivity Assays

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Defines Oscar Health's coverage stance for in vitro laboratory assays that test tumor sensitivity or resistance to chemotherapy agents and describes applicability, limitations, and supporting background for providers seeking reimbursement.

Policy Summary

PayerOscar Health

PolicyIn Vitro Chemoresistance and Chemosensitivity Assays

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateOct 1, 2026

Last ReviewJun 16, 2026

Next Review DateJun 16, 2026

Key ActionConfirm member benefits and obtain prior authorization when billing proprietary/PLA or unlisted pathology codes; ensure documentation supports the medical necessity and test method.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

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CurrentOscar HealthPolicy N/A

In Vitro Chemoresistance and Chemosensitivity Assays

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Sign up for all Oscar Health policy alerts

Know when Oscar Health releases new policies or updates existing guidance.

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Policy Summary

PayerOscar Health

PolicyIn Vitro Chemoresistance and Chemosensitivity Assays

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateOct 1, 2026

Last ReviewJun 16, 2026

Next Review DateJun 16, 2026

Key ActionConfirm member benefits and obtain prior authorization when billing proprietary/PLA or unlisted pathology codes; ensure documentation supports the medical necessity and test method.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2assay classes not meeting criteria

8procedure codes listed

~9proprietary tests referenced

9+evidence citations

Coverage Criteria

Not Medically Necessary

Not medically necessary / not covered

Not Covered Assays: In vitro chemosensitivity assays (e.g., histoculture drug response assay, fluorescent cytoprint assay) DO NOT MEET CRITERIA; In vitro chemoresistance assays (e.g., extreme drug resistance [EDR] assays) DO NOT MEET CRITERIA.

Policy states lack of available published scientific literature confirming the tests are required and beneficial for diagnosis and treatment.

The policy explicitly excludes in vitro chemosensitivity assays and in vitro chemoresistance assays from meeting coverage criteria. Oscar Health determined these assays do not meet criteria because there is a lack of available published scientific literature confirming that the tests are required and beneficial for diagnosis or treatment. Examples cited in the policy include the histoculture drug response assay and fluorescent cytoprint assay (chemosensitivity) and extreme drug resistance (EDR) assays (chemoresistance).

Laboratory-developed tests (LDTs) used to perform chemosensitivity or chemoresistance assays are not approved or cleared by the U.S. Food and Drug Administration. Such LDTs are regulated by CMS under CLIA as high-complexity laboratory tests; laboratories developing these in-house assays must validate and perform them internally. The policy notes that FDA clearance or approval is not currently required for clinical use of LDTs, but their regulatory status may affect coverage determinations.

The policy lists representative assay types and class examples to clarify scope. Named chemosensitivity assays include the histoculture drug response assay and the fluorescent cytoprint assay. Named chemoresistance assays include extreme drug resistance (EDR) assays. The document groups these and similar proprietary or non‑proprietary platforms under the broader categories of in vitro chemosensitivity and chemoresistance testing and treats them as not meeting coverage criteria.

Applicability

Applicability depends on the member's benefit coverage and may be superseded by applicable Medicare/Medicaid regulations.

Applicability: Application of criteria is dependent upon an individual's benefit coverage at the time of the request. Specifications pertaining to Medicare and Medicaid are found in the 'Applicable State and Federal Regulations' section of this policy document.

Coverage determinations should follow benefit documents and applicable state/federal rules.

Covered Indications

Oncology tumor-specific predictive testing

Examples of proprietary chemoresistance/chemosensitivity platforms and tumor types referenced in the policy (no positive coverage criteria are provided for these tests).

Proprietary/PLA assays and tumor examples: Proprietary tests listed include: Onco4D™ / 3D Predict Glioma (0248U) — oncology spheroid 3D culture, brain/glioma; Theralink® RPPA (0249U) — semiquantitative phosphoprotein analysis; ChemoID® (0435U) — chemotherapeutic cytotoxicity assay of cancer stem cells reported categorically; 3D PredictTM Ovarian / ChemoID® reporting (0525U) — ovarian/fallopian/peritoneal response prediction. These are presented with PLA codes and associated tumor types but the policy does not provide explicit coverage criteria for them.

Providers should refer to benefit coverage and prior authorization processes; these assays are nevertheless within the class of chemosensitivity/chemoresistance tests that the policy identifies as not meeting criteria.

Not Covered

Not covered: In vitro chemosensitivity assays and in vitro chemoresistance assays do not meet coverage criteria and are considered not medically necessary due to insufficient published evidence demonstrating they are required and beneficial for patient diagnosis or treatment. This exclusion applies to the assay classes named in the policy.

Additional context: the policy highlights that many assays for predicting tumor drug response are offered as laboratory‑developed tests. Because LDTs are not FDA-approved or cleared and are regulated under CLIA as high-complexity tests, their in‑house status and lack of FDA review are factors that inform coverage determinations; providers should be aware this regulatory classification may influence reimbursement and medical‑necessity review.

Coding

Applicable CPT/HCPCS Procedure CodesCPT

86849	Unlisted immunology procedure.
88104	Cytopathology, fluids, washings or brushings, except cervical or vaginal; smears with interpretation.
88199	Unlisted cytopathology procedure.
88305	Level IV - Surgical pathology, gross and microscopic examination.
88313	Special stain including interpretation and report; Group II, all other (eg, iron, trichrome), except stain for microorganisms, stains for enzyme constituents, or immunocytochemistry and immunohistochemistry.
88358	Morphometric analysis; tumor (eg, DNA ploidy).
89050	Cell count, miscellaneous body fluids (eg, cerebrospinal fluid, joint fluid), except blood.
89240	Unlisted miscellaneous pathology test.

Procedure codes (examples)CPT

86849	Unlisted immunology procedure.
88104	Cytopathology, fluids, washings or brushings, except cervical or vaginal; smears with interpretation.
88199	Unlisted cytopathology procedure.
88305	Level IV - Surgical pathology, gross and microscopic examination.
88313	Special stain including interpretation and report; Group II, all other (eg, iron, trichrome), except stain for microorganisms, stains for enzyme constituents, or immunocytochemistry and immunohistochemistry.
88358	Morphometric analysis; tumor (eg, DNA ploidy).
89050	Cell count, miscellaneous body fluids (eg, cerebrospinal fluid, joint fluid), except blood.
89240	Unlisted miscellaneous pathology test.

Proprietary/PLA codesHCPCS

0248U	Proprietary test: 3D Predict Glioma / Onco4D™ (examples listed); proprietary oncology predictive assays (PLA code).
0249U	Proprietary test: Theralink® Reverse Phase Protein Array (RPPA) — proprietary oncology assay (PLA code).
0435U	Proprietary test: ChemoID® (cytotoxicity assay of cancer stem cells) — proprietary oncology assay (PLA code).
0525U	Proprietary test: 3D PredictTM Ovarian / ChemoID® reporting (PLA code).

Provider Actions & Billing Guidance

Prior Authorization

Authorization depends on member benefits and medical necessity

Coverage and any authorization are determined by the member's benefit plan and medical necessity guidelines; the specific assays listed in this policy do not meet criteria and are unlikely to be approved for coverage.

Services must meet authorization and medical necessity guidelines for the procedure, diagnosis, and member's state of residence.
The policy states: “In vitro chemosensitivity assays … DO NOT MEET CRITERIA” and “In vitro chemoresistance assays … DO NOT MEET CRITERIA.”

Prior Authorization

Check prior authorization for PLA / unlisted pathology codes

Certain proprietary (PLA) or unlisted pathology/immunology procedure codes may require prior authorization — confirm payer-specific PA rules before ordering or billing when using these codes.

PLA codes listed include examples such as 0248U, 0249U, 0435U, 0525U.
Unlisted or pathology codes in CPT (e.g., 86849, 88199, 89240) are referenced in the policy and may have payer PA requirements.

Ordering Requirements

Step Therapy

Follow member benefit and authorization processes when ordering

Ordering, authorization, and coverage determinations depend on the member’s benefit coverage and medical necessity; providers must follow the payer’s authorization processes and benefit documents when ordering tests.

“Application of criteria is dependent upon an individual's benefit coverage at the time of the request.”
Providers should consult member benefit documents and follow authorization processes.

Documentation Required

Order only CLIA‑validated in‑house LDTs and document validation

If ordering a laboratory‑developed test, ensure the test is validated and performed in‑house under CLIA '88 high‑complexity requirements before submission for reimbursement.

“These laboratory‑developed tests (LDTs) are regulated … as high‑complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88).”

Definitions

Definition — EDR

EDR (Extreme Drug Resistance)Assay exposing cultured tumor cells to high drug concentrations and prolonged exposure to identify drugs of least clinical benefit (extreme drug resistance).

Definition — ATP-TCA

ATP-TCA (Adenosine triphosphate–tumor chemosensitivity assay)An assay that measures cellular adenosine triphosphate (ATP) as a marker of tumor cell viability after exposure to chemotherapeutic agents to assess chemosensitivity.

Definition — Laboratory‑Developed Test (LDT)

Laboratory-Developed Test (LDT)An in‑house clinical test developed and validated by the performing laboratory and regulated by CMS as a CLIA '88 high‑complexity test; LDTs are not approved or cleared by the U.S. Food and Drug Administration (FDA).

Background

Background: In vitro chemosensitivity and chemoresistance assays are laboratory techniques intended to evaluate how a patient’s tumor cells respond to chemotherapeutic agents ex vivo. Tumor cells are cultured outside the body and exposed to drugs to assess cell survival, death, or other viability measures; examples named in the policy include assays such as histoculture drug response and fluorescent cytoprint, as well as EDR methods. While various proprietary and non‑proprietary platforms exist, the policy notes that available published literature does not sufficiently demonstrate that using these assays to guide therapy improves diagnosis or treatment outcomes.

Policy Summary

PayerOscar Health

PolicyIn Vitro Chemoresistance and Chemosensitivity Assays

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateOct 1, 2026

Last ReviewJun 16, 2026

Next Review DateJun 16, 2026

Key ActionConfirm member benefits and obtain prior authorization when billing proprietary/PLA or unlisted pathology codes; ensure documentation supports the medical necessity and test method.

SourceLink

On This Page

Note

Follow authorization process and document medical necessity

Providers must follow the policy’s authorization processes and submit documentation demonstrating medical necessity; claims will be evaluated against member benefits and authorization rules.

Oscar’s reimbursement policies require services to meet authorization and medical necessity guidelines for the procedure, diagnosis, and member's state of residence.
Providers are responsible for accurate claims submission and documentation.

Note

Ensure CLIA validation and in‑house performance for LDTs

Laboratory-developed tests (LDTs) are regulated under CLIA as high‑complexity tests and are not FDA‑approved or cleared; providers using LDTs must ensure compliance with CLIA validation and in‑house performance requirements.

“These laboratory‑developed tests (LDTs) are regulated by the Centers for Medicare and Medicaid (CMS) as high‑complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88).”
LDTs are not approved or cleared by the U.S. Food and Drug Administration.

Documentation Required

Provide accurate documentation and ensure LDT validation

Submit accurate, complete documentation supporting the tests performed; the laboratory performing an LDT must validate the test and retain validation records.

Providers are responsible for submission of accurate documentation of services performed and coding according to industry standards.
LDTs “must validate and perform in house” and are regulated as CLIA high‑complexity tests.

Documentation Required

Include method, specimen type, and interpretive details in documentation

Documentation must support the use of an LDT or proprietary assay, including the testing method, specimen type, and interpretive report details consistent with any listed CPT/HCPCS or PLA code.

Documentation should include method, specimen type, and interpretive report details consistent with listed CPT/HCPCS or PLA codes.
Policy notes proprietary assays and PLA codes (e.g., ChemoID®, 3D Predict Glioma) that require appropriate supportive documentation.

Denial Risk

Noncompliance with coding/billing may lead to denial or recoupment

Claims may be denied or payments recouped if coding, billing guidelines, or current reimbursement policies are not followed; code and documentation must align with industry standards.

Claims should be coded per CPT, HCPCS, ICD‑10, CMS NCCI, and other industry standards.
The policy states: “If appropriate coding/billing guidelines or current reimbursement policies are not followed, we may deny the claim and/or recoup claim payment.”

Denial Risk

In vitro chemosensitivity and chemoresistance assays are not covered

Assays categorized as in vitro chemosensitivity or in vitro chemoresistance (including extreme drug resistance assays) do not meet criteria and are not covered under this policy.

Policy explicitly: “In vitro chemosensitivity assays … DO NOT MEET CRITERIA.”
Policy explicitly: “In vitro chemoresistance assays (e.g., extreme drug resistance [EDR] assays) DO NOT MEET CRITERIA.”

Billing Rule

Unlisted procedure codes may trigger review or denial

Use of unlisted procedure codes (for example 86849, 88199, 89240) or other pathology/unlisted immunology codes may trigger coding review and potential denial if documentation does not support billed services.

Applicable CPT examples include 86849, 88199, 89240 (unlisted immunology/cytopathology/miscellaneous pathology tests).
The policy warns that inappropriate coding/billing may result in claim denial or recoupment.

LDTs must be validated and performed in house by the laboratory.