CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

In vitro chemosensitivity and chemoresistance assays

This policy governs coverage and medical necessity determination for in vitro chemosensitivity and chemoresistance assays used to predict tumor response to chemotherapy for Blue Cross Blue Shield - Rhode Island members.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyIn vitro chemosensitivity and chemoresistance assays

Policy CodePolicy N/A

Change TypeNo material change

Effective Date09/04/2007

Next Review DateN/A

Key ActionDo not bill members for these assays unless the member was informed and agreed in writing to proceed at their own expense.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Not coveredCoverage stance

Insufficient evidenceRationale

81535/81536CPT codes cited

~25References

3Publisher notes

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.

Not Medically Necessary

Not covered / Not medically necessary — Covered when NONE of the following are true (expressed as an exclusion):

Policy coverage determination: In vitro chemosensitivity assays and chemoresistance assays are considered not covered / not medically necessary because the evidence is insufficient to determine the effects of the technology on health outcomes.

No criteria are provided under which these assays would be considered medically necessary.

In vitro chemosensitivity assays and chemoresistance assays are not covered by this policy and are considered not medically necessary.

The available evidence is insufficient to determine the effects of these technologies on health outcomes, and therefore assay-directed chemotherapy selection has not been demonstrated to provide clinically meaningful benefit.

Benefits and eligibility for services are determined by the member's subscriber agreement, member certificate, or employer agreement, which supersede this medical policy; contact the provider call center for member-specific benefit information.

This section does not itself constitute a determination of benefits or medical necessity for a particular member; providers should refer to the member’s contract language and participation agreements for applicable coverage and billing rules, including requirements for written member consent when services are non-covered.

Billing and CPT Codes

Covered CPT Codes (listed)CPTNot Covered

81535

Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by DAPI stand and morphology, predictive algorithm reported as a drug response score; first single Or drug combination drug

Not covered / not medically necessaryCPTNot Covered

81536

Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by DAPI stand and morphology, predictive algorithm reported as a drug response score; each additional single or drug combination (List separately in addition to code for primary procedure) drug

Not covered / not medically necessaryCPTNot Covered

81536

Other assaysmixedNot Covered

No codes listed

Provider Requirements and Billing Guidance

Prior Authorization

Prior authorization and benefit variability

Prior authorization is not applicable for this policy. Benefits may vary by group or contract; providers must refer to the member's Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for applicable coverage.

Note

Prior authorization

This section contains no explicit prior authorization requirements.

Denial Risk

Member financial responsibility and denial risk

Claims determined to be not medically necessary (or services that are non-covered benefits) may not be billed to the member unless the provider has informed the member and obtained written agreement in advance to continue treatment at the member's expense. Refer to the provider participation agreement for applicable provisions.

Denial Risk

Coverage denial risk and verification

Claims for these assays are considered not medically necessary and are subject to denial. Providers should verify member-specific benefits and eligibility with the provider call center before rendering services.

Billing Rule

Claims coding note

There are no specific CPT codes for other assays; when appropriate, file claims using an unlisted code. The listed codes (e.g., 81535, 81536) are not covered for BlueCHiP for Medicare and are not medically necessary for Commercial Products.

Note

Benefit and eligibility verification

For member-specific benefits and eligibility, contact the provider call center prior to providing services.

Background

In vitro chemosensitivity and chemoresistance assays are laboratory tests that expose tumor cells to chemotherapeutic agents and quantify cell viability or death to infer likely tumor response. Methods include differential staining and dye-exclusion techniques, fluorometric assays, incorporation of radioactive precursors, colorimetric assays (e.g., Histoculture Drug Resistance assay), and ATP bioluminescence assays. A variety of commercial assays (for example, ChemoFx, HDRA, and Extreme Drug Resistance/EDR) are available, but assay methods and drug concentrations vary widely and clinical studies are inconsistent and insufficient to show that assay-directed therapy improves survival or other meaningful health outcomes.

Definitions

In vitro chemosensitivity/chemoresistance assays — methods and outcomes

Assay typesDifferential staining/dye exclusion, fluorometric microculture cytotoxicity, thymidine incorporation/EDR, colorimetric (HDRA), ATP bioluminescence

Specimen and culture methodologyTumor tissue is mechanically or enzymatically disaggregated to single cells or small aggregates and cultured as monolayers, spheroids, or 3‑D matrices depending on the assay (e.g., 50–100 cell spheroids for EVA/PCDTM)

Drug exposure and dosingCells are exposed to the chemotherapeutic agent(s) at multiple concentrations (commonly a physiologic dose, tenfold lower, and tenfold higher) with incubation times varying by assay (typical exposures 3–6 days reported)

Measured outcomesCell viability or death quantified by dye exclusion, fluorescent hydrolysis (fluorescein), radioactive thymidine incorporation, colorimetric mitochondrial enzyme activity, or ATP‑driven chemiluminescence; decreased viability indicates sensitivity and persistence of signal indicates resistance

Result interpretationAssays report relative sensitivity or resistance (e.g., thymidine incorporation levels above reference indicate resistance; ATP decrease indicates sensitivity); specific scoring/thresholds vary by assay and vendor

Examples of chemosensitivity/chemoresistance assays

ChemoFx (Helomics/Precision Therapeutics)An ATP‑based chemoluminescence assay that cultures tumor cells (monolayer) and quantifies ATP after drug exposure to report sensitivity/resistance

Extreme Drug Resistance (EDR/Oncotech)A thymidine incorporation–based assay measuring metabolic incorporation of tritiated thymidine; higher incorporation indicates chemoresistance

Additional examples / vendorsOther named assays include Histoculture Drug Resistance Assay (HDRA) using colorimetric mitochondrial assays and EVA/PCDTM assays using differential staining of spheroids