Chemoresistance and Chemosensitivity Assays
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This policy governs coverage and prior authorization for in vitro chemoresistance and chemosensitivity assays used to guide chemotherapy selection for members of Blue Cross Blue Shield - Rhode Island.
No material clinical or coverage changes in this revision.
Coverage Determinations and Policy Statements
Overall Coverage Determinations
Covered when ALL of the following are met:
Benefits may vary by group/contract; refer to the applicable Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for member-specific coverage determinations.
See Methods and Evidence discussion for assay-specific details (e.g., ATP-based assays and ChemoFX).
Some genetic testing services may be excluded for self-funded groups under the state Biomarker Testing Mandate. For group plans that have excluded expanded biomarker testing coverage, specific assay CPTs are listed in this policy as either not medically necessary or not covered. The policy explicitly names CPT 0564T and the ChemoFx® CPTs 81535 and 81536, and notes that there are no specific CPT codes for other assays; claims for assays without a specific CPT should be filed using an Unlisted CPT code.
Services that are determined to be not medically necessary or that are non-covered benefits are excluded from payment under the member’s subscriber or employer agreement. Providers should verify member-specific benefits via the provider call center and consult the applicable Benefit Booklet or subscriber agreement. If a service is not covered or not medically necessary, the provider may not bill the member unless the member provided written agreement in advance to accept financial responsibility.
For Commercial Products, in vitro chemosensitivity and chemoresistance assays are considered not medically necessary because the evidence is insufficient to demonstrate an improvement in net health outcomes.
When services are designated as not medically necessary or are non-covered benefits, they are excluded from payment and may not be billed to the member unless prior written consent is obtained. Benefits and eligibility are governed by the member’s subscriber agreement or employer agreement; providers should confirm coverage before services are rendered. The policy also identifies specific CPTs (for example, 0564T, 81535, 81536) and instructs that tests without a specific CPT should be submitted with an Unlisted CPT.
Applicable CPT and Billing Guidance
| 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 |
| 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 (List separately in addition to code for primary procedure) |
| Unlisted CPT | There are no specific CPT codes for other assays. Claims should be filed with an unlisted code. All Unlisted genetic testing CPT codes require prior authorization to determine the service rendered and whether it is covered or not medically necessary. |
Prior Authorization, Billing, and Provider Responsibilities
Prior Authorization Required
All Unlisted genetic testing CPT codes require prior authorization so the service can be identified and medical necessity determined. Prior authorization is required for unlisted or specified assay CPTs; if a laboratory service is provided without proper authorization it will be denied and the participating laboratory may be financially liable and may not bill the member.
- Unlisted genetic testing CPTs: ordering physician must obtain prior authorization
- Laboratories are prohibited from obtaining or participating in prior authorization on behalf of the ordering physician
- Unauthorized laboratory services will be denied and billed to the laboratory, not the member
- Improperly obtained third-party authorizations (including laboratory representatives) are considered violations and may result in sanctions, up to termination from the BCBSRI network
Prior Authorization / Payment Confirmation
Confirm member benefits and eligibility with BCBSRI prior to rendering services. Benefits and eligibility are determined by the member's subscriber agreement, certificate, and/or employer agreement; those governing documents supersede this policy. For member-specific benefits, contact the provider call center.
- Verify coverage and prior authorization requirements through the BCBSRI provider call center before testing
- If services are determined not medically necessary or are non-covered benefits, the provider may not charge the member unless the member was informed and provided written agreement in advance
Provider Responsibility for Authorization
Only the ordering physician may pursue and obtain prior authorization, submit appeals, and handle administrative processes related to medical necessity determinations. Laboratories and laboratory representatives are not allowed to obtain authorizations or participate in the authorization or appeal process on behalf of the ordering physician.
- Ordering physician must be the party to request authorization and manage appeals
- Do not use laboratory representatives or third parties to obtain or facilitate authorizations or appeals
- Documentation submitted for authorization must be prepared and submitted by the ordering physician (not by a laboratory or its representative)
Unauthorized Laboratory Services Denied
If a laboratory provides a service that has not been authorized, the service will be denied and the financial liability will fall to the participating laboratory; the laboratory may not bill the member. BCBSRI may sanction providers who circumvent the authorization process.
- Unauthorized services = denial and laboratory financial liability
- Circumventing authorization (including third-party obtained authorizations) may result in sanctions or termination
Unlisted CPTs and Ordering Physician Actions
Claims for assays without specific CPT codes should be filed using an Unlisted CPT code. The ordering physician is responsible for obtaining prior authorization for unlisted genetic testing CPTs to identify the service and support medical necessity.
- File claims for assays without specific CPTs using the appropriate Unlisted CPT
- Ordering physician must pursue prior authorization for Unlisted genetic testing CPTs
Benefits Verification and Governing Documents
Verify benefits and eligibility via the provider call center; subscriber agreements and employer documents govern coverage decisions. This policy is informational and not a guarantee of payment. BCBSRI may revise the policy at any time.
- Verify member-specific benefits and any prior authorization requirements through BCBSRI provider call center
- Refer to subscriber and participation agreements for billing and member financial responsibility rules
Denial Risk for Non‑Medically Necessary Services
Services determined to be not medically necessary or non-covered may be denied and subject to provider billing restrictions. Providers must obtain necessary authorizations and follow the required process to avoid claim denials and potential restrictions on billing members.
- Denial risk exists for services lacking medical necessity or required authorization
- Provider billing restrictions may apply if authorization process is not followed
Clinical Background and Rationale
In vitro chemoresistance and chemosensitivity assays expose a patient’s tumor cells to chemotherapeutic agents in culture and measure cell viability or death to estimate the tumor’s responsiveness to specific drugs. Methods vary and include differential staining/dye exclusion techniques, ATP-based chemoluminescent assays, and other viability or apoptosis-based assays. While these assays aim to predict which agents may be effective, published evidence consists largely of correlational studies and limited randomized trials and does not consistently demonstrate that assay-directed therapy improves survival or other net health outcomes. Consequently, these technologies are considered investigational or not medically necessary in many benefit contexts.
Terms and Test Examples
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