CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

In vitro chemosensitivity and chemoresistance assays — Coverage Criteria

This policy governs coverage determinations for in vitro chemosensitivity and chemoresistance assays used to predict tumor responsiveness to chemotherapeutic agents for Blue Cross Blue Shield - Rhode Island members, including Commercial and BlueCHiP for Medicare products.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyIn vitro chemosensitivity and chemoresistance assays — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateApr 9, 2007

Next Review DateN/A

Key ActionDo not bill CPT codes 81535 or 81536; these are listed as not covered and claims will be denied.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Not coveredBlueCHiP for Medicare stance

Not medically necessaryCommercial products stance

2 codesSpecific CPT codes not covered

NonePrior authorization

Insufficient evidencePrimary reason for noncoverage

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Coverage Determination

Coverage stance

Coverage determination by product:

BlueCHiP for Medicare: In vitro chemosensitivity assays and chemoresistance assays are not covered because the evidence is insufficient to determine effects on health outcomes.

Commercial Products: In vitro chemosensitivity assays and chemoresistance assays are considered not medically necessary because the evidence is insufficient to determine effects on health outcomes.

Benefits for in vitro chemosensitivity and chemoresistance assays may vary between groups or contracts. Refer to the member's Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for the applicable coverage determination and any contract-specific provisions.

Services determined to be not medically necessary or to be non-covered benefits are exclusions from payment. Providers should verify member eligibility and benefit design before performing such services and must obtain written member agreement in advance if charging the member for services that are determined to be not medically necessary or non-covered.

For Commercial Products, in vitro chemosensitivity and chemoresistance assays are considered not medically necessary. The available evidence, including randomized and nonrandomized studies as well as correlational observational data, is insufficient to demonstrate that assay-directed therapy improves survival or other patient-important outcomes; therefore the tests are not supported for routine clinical use to guide chemotherapy selection.

When a service is determined to be not medically necessary, it may not be payable under the member's contract. Providers may not bill members for such services unless the member has been informed and has provided written agreement to pay in advance.

Coding and Billing

Not covered CPT CodesCPTNot 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 drug or drug combination
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 drug or drug combination (List separately in addition to code for primary procedure)

Other assaysmixed

No codes listed

Other assaysmixed

No codes listed

Provider Actions, Prior Authorization & Billing

Prior Authorization

Not applicable

Documentation Required

Benefit Verification

Benefits may vary by contract. Verify member-specific benefits, eligibility, and coverage determinations by reviewing the member's Benefit Booklet, Evidence of Coverage or Subscriber Agreement or by contacting the provider call center.

Step Therapy

Step therapy / Utilization

Step therapy / utilization requirements are not specified in this policy. Utilization management, step therapy, or quantity limits may vary by contract; refer to the member's benefit documents or contact the provider call center for any applicable requirements.

Background

In vitro chemosensitivity and chemoresistance assays are laboratory tests that expose a patient's tumor cells to chemotherapeutic agents in vitro and measure cell viability or death using a variety of methods (for example, differential staining/dye exclusion, radioactive precursor incorporation, colorimetric assays such as the HDRA, and ATP bioluminescence). The assays aim to infer likely clinical response by quantifying drug-induced cell death or apoptosis, but methods, drug concentrations, and incubation conditions vary across assays and commercial tests.

Key Definitions

In vitro chemosensitivity/chemoresistance assay — definition and test characteristics (methods, endpoints)

DefinitionLaboratory tests that expose a patient’s tumor cells to chemotherapeutic agents in vitro and measure cell viability or death to infer likely clinical response.

Common assay methodsDifferential staining/dye exclusion (e.g., Differential Staining Cytotoxicity, EVA/PCD), radioactive precursor incorporation (tritiated thymidine, EDR), colorimetric mitochondrial assays (HDRA), and ATP bioluminescence assays (e.g., ChemoFX).

Specimen and culture characteristicsSpecimens are typically disaggregated from surgical or biopsy tissue to single cells or small spheroids; some assays use 3‑dimensional microaggregates (50–100 cell spheroids) while others grow cells in monolayer or soft agar cultures.

Drug exposure and dosing variabilityAssay drug concentrations and exposure times vary widely by tumor type and assay; reported approaches include multiple dose levels (e.g., physiologic, 10‑fold lower, 10‑fold higher) with incubation periods from days (commonly 3–6 days) to longer depending on method.

Primary endpoints / readoutsEndpoints include measures of cell death or viability such as differential dye uptake, incorporation of radioactive precursors, changes in optical density over time, colorimetric mitochondrial activity, and ATP‑linked luminescence as proxies for chemosensitivity or chemoresistance.

Line of Therapy

any

Use at initiation of chemotherapy: Assays are described in the context of patients who are initiating chemotherapy, but evidence is insufficient to support clinical benefit when used to select therapy.

Regimen Selection

Regimen/Intervention	Coverage status	Rationale / policy text
Any regimen selection guided by in vitro chemosensitivity or chemoresistance assay results (assay-directed selection of chemotherapeutic agents)
Not covered / Not medically necessary
In vitro chemosensitivity and chemoresistance assays are not covered for BlueCHiP for Medicare and are considered not medically necessary for Commercial products because the evidence is insufficient to determine effects on health outcomes; assay-directed selection of chemotherapy has not consistently demonstrated improved survival or other patient-important outcomes.