Modifiedblue cross blue shield - louisianaPolicy AHS - G2100 - In Vitro Chemoresistance and Chemosensitivity Assays

G2100: In Vitro Chemoresistance and Chemosensitivity Assays

This policy defines Blue Cross and Blue Shield of Louisiana's coverage stance and limitations for in vitro chemotherapy sensitivity and resistance assays (proprietary and non-proprietary), lists applicable CPT/HCPCS codes, summarizes evidence and guideline positions, and records revision history and regulatory applicability.

Policy Summary

Payerblue cross blue shield - louisiana

PolicyG2100: In Vitro Chemoresistance and Chemosensitivity Assays

Policy CodePolicy AHS - G2100 - In Vitro Chemoresistance and Chemosensitivity Assays

Change TypeReviewed and Updated

Effective DateFeb 1, 2026

Next Review Date

Key ActionDetermine member's benefit coverage at time of request; if Medicare/Medicaid, follow applicable government/local coverage determinations which supersede this policy.

SourceLink

POLICY UPDATE CHANGES

02/01/2026 - Reviewed and Updated: Updated the background, guidelines and recommendations, and evidence-based scientific references; literature review did not necessitate modifications to coverage criteria.

01/01/2025 - Reviewed and Updated: Updated background, guidelines and references; added CPT code 0525U.

10/01/2024 - Off-Cycle Coding Modification: Updated test descriptor for CPT code 0248U.

07/01/2024 - Client Requested Variance: Removal of code 0285U.

05/01/2024 - Reviewed and Updated: Edits for clarity; literature review did not necessitate modifications to coverage criteria.

01/01/2024 - Off-Cycle Coding Modification: Added CPT code 0435U.

04/01/2023 - Off-Cycle Coding Modification: Removed deleted PLA codes 0324U, 0325U.

03/10/2023 - Added CPT codes 0249U, 0285U, 0324U, and 0325U.

05/15/2022 - Initial Policy Implementation

2Assay types explicitly not covered

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Coverage Summary

Scope: This policy (Policy Number: AHS - G2100 - In Vitro Chemoresistance and Chemosensitivity Assays) defines Blue Cross and Blue Shield of Louisiana's coverage stance and limitations for in vitro chemotherapy sensitivity and resistance assays (proprietary and non-proprietary), lists applicable CPT/HCPCS codes, summarizes evidence and guideline positions, and records revision history and regulatory applicability. Effective date: 02/01/2026. Last review: 02/01/2026.

Coverage stance: Does not meet coverage criteria / not covered — the policy specifies that these assays do not meet coverage criteria because published scientific literature does not confirm that test use is required and beneficial for diagnosis or treatment.

Policy facts

Policy numberAHS - G2100 - In Vitro Chemoresistance and Chemosensitivity Assays

Policy titleIn Vitro Chemoresistance and Chemosensitivity Assays

PayerBlue Cross and Blue Shield - Louisiana

Effective date02/01/2026

Last review02/01/2026

Coverage stanceDoes not meet coverage criteria / Not covered

Medical Necessity / Coverage Determinations

Coverage Determination

The following tests do not meet coverage criteria due to lack of published scientific literature confirming clinical benefit:

ALL of the following

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

Applicable / Referenced Codes

Applicable / referenced CPT/HCPCS codesmixed

81535	Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by DAPI stain and morphology, predictive algorithm reported as a drug response score; first single drug or drug combination. Proprietary test: ChemoFX® Lab/manufacturer: Helomics, Corp.
81536	Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by DAPI stain and morphology, predictive algorithm reported as a drug response score; each additional single drug or drug combination.
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.
0083U	Oncology, response to chemotherapy drugs using motility contrast tomography, fresh or frozen tissue, reported as likelihood of sensitivity or resistance to drugs or drug combinations. Proprietary test: Onco4D™ Lab/manufacturer: Animated Dynamics, Inc.
0248U	Oncology spheroid cell culture in 3D microenvironment, 12 drug panel, brain or brain metastasis response prediction for each drug. Proprietary test: 3D Predict Glioma Lab/Manufacturer: KIYATEC®, Inc.

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Provider Actions & Billing Impact

Documentation Required

Benefit and regulation check

Determine member's benefit coverage at time of request; if Medicare/Medicaid, follow applicable government/local coverage determinations which supersede this policy.

If Medicare/Medicaid, follow applicable government/local coverage determinations which supersede this policy.

Denial Risk

Coverage exclusion

Claims for in vitro chemosensitivity and chemoresistance assays (including named example assays) do not meet coverage criteria and are subject to denial.

81535
81536

Background & Evidence Summary

Background / Rationale: In vitro chemosensitivity and chemoresistance assays evaluate tumor cell response to chemotherapeutic agents using patient-derived cells and a variety of assay techniques, including proprietary tests (for example, ChemoFX®, ChemoINTEL, KIYATEC 3D platforms) and non-proprietary methods (for example, MTT, ATP-TCA, DISC).

Although multiple assay types exist and several observational and prospective studies report correlations between assay results and clinical outcomes, the evidence is insufficient to demonstrate that use of these tests improves diagnosis or changes treatment decision-making in a way that yields validated clinical benefit.

Guideline positions: The ASCO 2011 guideline update states that use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents is not recommended outside of the clinical trial setting. NCCN guidance for ovarian cancer notes that chemosensitivity/resistance assays are being used at some centers but that the current level of evidence is not sufficient to supplant standard of care (category 3 recommendation).

Source	Summary
ASCO guideline (2011)	Not recommended outside clinical trials; oncologists should base chemotherapy on published clinical trials and patient factors; participation in trials evaluating these technologies encouraged.
NCCN (Ovarian Cancer)	Chemosensitivity/resistance assays are used at some institutions but current evidence is insufficient to replace standard-of-care chemotherapy (category 3 recommendation).
Policy coverage determination	In vitro chemosensitivity assays (e.g., histoculture drug response assay, fluorescent cytoprint) and in vitro chemoresistance assays (e.g., EDR) do NOT meet coverage criteria due to lack of published evidence confirming clinical benefit.
Selected observational/prospective studies	Mixed and limited evidence: some studies report correlations between assay results and outcomes (improved PFS/OS or predictive associations) but large prospective trials demonstrating clinical benefit and impact on survival are lacking.
Applicable CPT/HCPCS codes	Lists multiple proprietary and non-proprietary assay codes (examples: 81535/81536 ChemoFX, 0083U Onco4D, 0248U/0525U KIYATEC 3D Predict, 0435U/0564T ChemoID) referenced for denial/claims handling.
Revision history	Policy reviewed and updated (most recent 02/01/2026); literature reviews did not change coverage criteria; CPT code additions/updates noted (e.g., 0525U added 01/01/2025).

Definitions

EDRExtreme drug resistance assay

ChemoFX®Proprietary ex vivo chemosensitivity assay by Helomics

LDT

Not Covered / Experimental Assays

Per the Coverage Determination: the following tests and test types do not meet coverage criteria and are excluded from coverage under this policy.

Explicit statement: In vitro chemosensitivity and chemoresistance assays (proprietary and non-proprietary) do not meet coverage criteria, as described in the policy (the following examples are explicitly listed as not meeting coverage criteria: in vitro chemosensitivity assays such as histoculture drug response assay and fluorescent cytoprint assay; in vitro chemoresistance assays such as extreme drug resistance [EDR] assays).

Coverage Determination — Example assays not covered

For clarity, examples of named assays and assay types that do not meet coverage criteria include both proprietary and non-proprietary tests:

ALL of the following

In vitro chemosensitivity assay examples: In vitro chemosensitivity assays (examples: histoculture drug response assay [HDRA], fluorescent cytoprint assay, MTT, ATP-TCA, DISC, ChemoFX®, ChemoINTEL®) DO NOT MEET COVERAGE CRITERIA.
In vitro chemoresistance assay examples:

Revision History

02/01/2026revisedLatest

01/01/2025revised

01/01/2025 - Reviewed and Updated: Updated background, guidelines and references; added CPT code 0525U.

10/01/2024revised

10/01/2024 - Off-Cycle Coding Modification: Updated test descriptor for CPT code 0248U.