CurrentCignaPolicy 0203

Tumor In Vitro Chemosensitivity and Chemoresistance Assays

Defines coverage stance for in vitro tumor chemosensitivity and chemoresistance assays (CSRAs) for Cigna-administered health benefit plans; intended for laboratory/pathology, oncology providers and billing/operations staff.

Policy Summary

PayerCigna

PolicyTumor In Vitro Chemosensitivity and Chemoresistance Assays

Policy CodePolicy 0203

Change TypeAdministrative (no clinical changes)

Effective DateMay 15, 2025

Next Review DateMay 15, 2026

Key ActionWhen billing, providers must use the most appropriate codes as of the date of service and understand claims for CSRAs used to select chemotherapy outside of clinical trials are at risk for denial as investigational/unproven.

SourceLink

POLICY UPDATE CHANGES

Annual and focused reviews completed with 'No clinical policy statement changes.' (5/15/2025; 2/15/2025; 5/15/2024).

0203policy identifier

2025-05-15effective date

2026-05-15next review date

Experimentaloverall coverage decision

Multiple

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage determination for tumor in vitro chemosensitivity and chemoresistance assays

Not Covered / Experimental or Investigational

Tumor in vitro chemosensitivity or chemoresistance assays are considered experimental, investigational or unproven.

ALL of the following

Any tumor in vitro chemosensitivity or chemoresistance assay (including, but not limited to: EDR assays, MTT/MTS assays, ChemoFX, CorrectChemo/MiCK, FCCA, ATP assays, HDRA, fluorescence/cytoprint, differential staining cytotoxicity, HTCA, human tumor cloning assays, ex vivo 3D platforms, RPPA, ChemoID) is considered experimental, investigational or unproven
Assays proposed to guide selection of chemotherapy agents for individual patients outside of clinical trials are not established as clinically useful due to insufficient evidence of improved health outcomes (including overall survival, progression-free survival), lack of randomized controlled trials, and limitations in existing studies
Professional society guidelines (e.g., NCCN, ASCO) do not endorse routine clinical use of CSRAs to select chemotherapeutic agents; ASCO does not recommend use outside clinical trials

Considered Experimental/Investigational/Unproven

The following assays are considered experimental, investigational, or unproven because evidence is insufficient to demonstrate improved health outcomes (particularly overall survival) when therapy is directed by these assays:

ALL of the following

In vitro chemosensitivity and chemoresistance assays (CSRAs) including, but not limited to ATP-based assays (ATP-CRA), MTS/MTT assays, Histoculture Drug Response Assay (HDRA), ex vivo 3D cell culture platforms, Reverse Phase Protein Array (RPPA)-linked assays, cancer stem cell assays, and other tumor drug-response assays
Specific named/proprietary CPT/CPT-like or miscellaneous procedure codes identified in this policy (e.g., 81535, 81536, 0174U, 0248U, 0249U, 0525U, 0564T [deleted 12/31/2024]) are considered experimental/investigational when used to report these assays
Use of these assays to select chemotherapy regimens for individual patients is not recommended outside clinical trials (per ASCO and summarized evidence).

ChemoID / CSC and bulk tumor assay suggested thresholds (study-specific)CSC cell kill > 40%; bulk tumor cell kill > 55% (reported as associated with better outcomes in one small study)

Codes referenced and administrative coding notes

Considered Experimental/Investigational/Unproven - procedure codesCPT|HCPCS|CPT-ADJNot Covered

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.
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.
0174U	Oncology (solid tumor), mass spectrometric 30 protein targets, formalin-fixed paraffin-embedded tissue, prognostic and predictive algorithm reported as likely, unlikely, or uncertain benefit of 39 chemotherapy and targeted therapeutic oncology agents.
0248U	Oncology, spheroid cell culture in a 3D microenvironment, 12-drug panel, brain- or brain metastasis-response prediction for each drug.
0249U	Oncology (breast), semiquantitative analysis of 32 phosphoproteins and protein analytes, includes laser capture microdissection, with algorithmic analysis and interpretative report.
0525U	Oncology, spheroid cell culture, 11-drug panel (carboplatin, docetaxel, doxorubicin, etoposide, gemcitabine, niraparib, olaparib, paclitaxel, rucaparib, topotecan, veliparib) ovarian, fallopian, or peritoneal response prediction for each drug.
0564T	Oncology, chemotherapeutic drug cytotoxicity assay of cancer stem cells (CSCs), from cultured CSCs and primary tumor cells, categorical drug response reported based on percent of cytotoxicity observed, a minimum of 14 drugs or drug combinations (Code deleted 12/31/2024).

Coding Information (placeholder — codes referenced in policy header/body to be listed in Part 2)mixed

No codes listed

Administrative / coding notesmixed

deleted

0564T noted as deleted effective 12/31/2024.

Billing, documentation, and utilization guidance for providers

Documentation Required

Use of most appropriate billing codes

When billing, providers must use the most appropriate codes as of the date of service; services billed without covered diagnosis/procedure codes under this Coverage Policy will be denied as not covered.

Prior Authorization

Potential utilization review

Certain Cigna companies and/or lines of business only provide utilization review services and do not make coverage determinations; requests should be reviewed on an individual merits basis considering the applicable plan language and laws.

Clinical and evidence summary

In vitro chemosensitivity and chemoresistance assays (CSRAs) analyze tumor cells cultured from patient specimens and expose them to chemotherapeutic agents to predict tumor cell sensitivity or resistance. Techniques described in the policy include Extreme Drug Resistance (EDR) assays, MTT/MTS assays, ChemoFX (tumor drug response testing), MiCK/CorrectChemo (microculture kinetic apoptosis assays), Flow Cytometric Chemosensitivity Assay (FCCA), Fluorescence/cytoprint and differential staining cytotoxicity assays, ATP-based assays (including ATP-CRA), Histoculture Drug Response Assay (HDRA), and additional methods such as human tumor cloning/stem cell assays. Newer approaches noted include ex vivo 3D cell culture platforms and assays that incorporate Reverse Phase Protein Array (RPPA) analysis to measure protein target abundance and signaling activation. (These assay types are summarized in the policy list of testing methods and definitions.)

Defined terms

Definitions

CSRAChemosensitivity and chemoresistance assay — an in vitro laboratory test using tumor cells to predict response to chemotherapeutic agents.

EDRExtreme Drug Resistance assay — exposes tumor cells to high drug concentrations to identify survival indicating extreme resistance.

ChemoFXA commercial tumor drug response assay (Helomics / Predictive Oncology) that tests multiple agents and reports sensitivity/resistance.

MiCK / CorrectChemoMicroculture Kinetic Assay of Apoptosis — measures extent of apoptosis after drug exposure.

FCCAFlow Cytometric Chemosensitivity Assay — evaluates viability after drug exposure using flow cytometry.

ATP assayAdenosine Triphosphate-based assay — measures ATP as a marker of cell viability after drug exposure.

Policy changes and administrative notes

2025-05-15administrativeLatest

Annual review completed with no clinical policy statement changes.

2025-02-15administrative

Focused review completed with no clinical policy statement changes.

2024-05-15administrative

Annual review completed with no clinical policy statement changes.