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A.2.04.153
This policy addresses the use of tumor-informed circulating tumor DNA (ctDNA) testing for cancer management. The purpose of tumor-informed ctDNA testing in individuals with cancer is to predict disease course to inform treatment decisions and to monitor for recurrence following treatment.
Signatera
Signatera is a tumor-specific ctDNA test. Tumor tissue obtained from either a diagnostic biopsy or surgically resected tissue is used to identify 16 single nucleotide variants found in the tumor but not in normal tissue and are likely to be present in all tumor cells regardless of tumor evolution. A custom assay of 16 tumor-specific clonal, somatic variants is generated for the individual and the resulting tumor signature can be monitored throughout the individual’s disease course. When the test is used for detection of recurrence following curative treatment, plasma samples with 2 or more out of these 16 variants detected above a predefined confidence threshold are deemed to be ctDNA-positive. When the test is used to monitor treatment response, evaluation is based on whether ctDNA levels increase or decrease from a baseline measurement. The test is intended to be used in conjunction with radiological assessment.
Signatera is a laboratory developed test regulated under CLIA. Signatera has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA), but has received 3 Breakthrough Device Designations from the FDA:
In May 2019, Signatera was granted a Breakthrough Device Designation (BDD) for the detection of ctDNA in localized or advanced colorectal cancer patients to optimize the use of chemotherapy alone or in combination with durvalumab.
A March 2021 press release announced that the FDA granted 2 additional Breakthrough Device Designations covering new intended uses.
Tumor-informed circulating tumor DNA testing (e.g., Signatera) is considered investigational for all indications.
None
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
11/01/2022: New policy added. Approved by the Medial Policy Advisory Committee.
06/01/2023: Code Reference section updated to add CPT code 0340U.
10/11/2023: Policy description updated. Policy statement unchanged.
11/11/2024: Policy reviewed; no changes.
12/19/2024: Code Reference section updated to add new CPT code 0530U effective 01/01/2025.
04/01/2025: Code Reference section updated to add new CPT code 0539U, effective 04/01/2025.
01/12/2026: Policy reviewed; no changes.
Blue Cross Blue Shield Association policy # 2.04.153
This may not be a comprehensive list of procedure codes applicable to this policy.
Investigational Codes
Code Number | Description |
CPT-4 | |
0340U | Oncology (pan-cancer), analysis of minimal residual disease (MRD) from plasma, with assays personalized to each patient based on prior next-generation sequencing of the patient's tumor and germline DNA, reported as absence or presence of MRD, with disease-burden correlation, if appropriate |
0530U | Oncology (pan-solid tumor), ctDNA, utilizing plasma, next-generation sequencing (NGS) of 77 genes, 8 fusions, microsatellite instability, and tumor mutation burden, interpretative report for single-nucleotide variants, copy number alterations, with therapy association |
0539U | Oncology (solid tumor), cell-free circulating tumor DNA (ctDNA), 152 genes, next-generation sequencing, interrogation for single-nucleotide variants, insertions/deletions, gene rearrangements, copy number alterations, and microsatellite instability, using whole-blood samples, mutations with clinical actionability reported as actionable variant (New 04/01/2025) |
81479 | Unlisted molecular pathology procedure |
HCPCS | |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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