Summary & Overview
CPT 0340U: Signatera™ ctDNA Minimal Residual Disease Test
CPT code 0340U designates Signatera™, a proprietary, personalized circulating tumor DNA (ctDNA) assay from Natera Inc. The test uses a cancer patient’s plasma specimen and a customized panel derived from prior tumor and germline next-generation sequencing to detect minimal residual disease (MRD). As a PLA code, 0340U is unique to a single manufacturer's assay and supports precision oncology workflows by enabling individualized monitoring for residual or recurrent disease.
This national overview addresses payer coverage patterns for major carriers, including Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find concise benchmarks on payer recognition of PLA tests, summaries of clinical context for MRD testing, and the policy and coding implications specific to a proprietary ctDNA assay. The publication outlines where payers have created coverage frameworks, highlights typical sites of service (clinical and hospital outpatient laboratories), and explains how CPT PLA coding signals a manufacturer-specific test versus broadly available assays.
The report provides practical information for billing and revenue cycle teams, laboratory administrators, and policy analysts: how 0340U is described in clinical terms, which payers are included in the review, and what topics are essential for contract and coding discussions. Data not available in the input are identified as such rather than inferred.
Billing Code Overview
CPT code 0340U is a Proprietary Laboratory Analyses (PLA) code that applies exclusively to Signatera™ from Natera Inc. The test analyzes a cancer patient’s plasma specimen using targeted sequencing of circulating tumor DNA (ctDNA) to evaluate minimal residual disease (MRD). The targeted sequences are customized based on a prior next-generation sequencing (NGS) analysis of the patient’s tumor and germline DNA, enabling a personalized assessment of tumor-derived DNA fragments in plasma.
Service type: Laboratory — proprietary, personalized ctDNA MRD testing
Typical site of service: Clinical laboratory or hospital outpatient laboratory using a patient plasma specimen
Data not available in the input.
Clinical & Coding Specifications
Clinical Context
A 58-year-old patient with stage II colon adenocarcinoma underwent surgical resection followed by adjuvant chemotherapy. After completion of therapy, the oncology team orders a personalized minimal residual disease (MRD) assay to monitor for molecular relapse. The test, Signatera™ (0340U), requires a baseline tumor tissue next-generation sequencing (NGS) profile and matched germline DNA to design a patient-specific ctDNA panel. A peripheral blood draw (plasma) is collected in a clinic or outpatient laboratory 2–6 weeks after surgery and then serially at defined surveillance intervals (for example every 3 months for the first 2 years). The clinical workflow includes: pre-test verification of prior tumor NGS and germline results, blood collection using cell-free DNA tubes, specimen shipping to Natera Inc., laboratory processing for targeted sequencing of personalized ctDNA markers, and reporting of qualitative and quantitative MRD results to the treating oncologist for surveillance and potential management decisions.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
00 | No modifier required / placeholder in some systems | Rarely used; included by some payors as default when no other modifier applies |
22 | Increased procedural services | Use when work or resources required for test documentation are substantially greater than typical (e.g., complex case coordination for customized assay design) |
26 | Professional component | Use if billing for professional interpretation separate from the performing laboratory (uncommon for PLA but applicable if independent professional interpretation is billed) |
52 | Reduced services | Use when the full test was not completed and a reduced version was provided |
53 | Discontinued procedure | Use if specimen collection could not be completed and the test was aborted before performance |
62 | Two surgeons / shared services | Not typically applicable to lab testing; included for completeness when surgical teams share billing related to pre-analytic procedures |
78 | Unplanned return to the operating/procedure room by same physician following initial procedure | Not applicable to this laboratory assay except in rare peri-procedural contexts |
80 | Assistant surgeon | Not applicable to lab testing; retained for systems that require selection |
82 | Assistant surgeon (when qualified resident not available) | Not applicable to lab testing |
AS | Physician assistant, nurse practitioner, or clinical nurse specialist services | Use when such practitioners perform specimen collection under their billing rules |
QK | Medical director clinical laboratory supervising test with high complexity | Use when a medical director provides clinical supervision beyond routine and separate reporting is required |
| Taxonomy Code | Specialty | Notes |
|---|---|---|
208000000X | Hematology & Oncology | Medical oncologists order and interpret MRD ctDNA assays for cancer surveillance |
207RC0000X | Anatomic/Clinical Pathology | Pathologists coordinate specimen handling and results integration with tumor NGS data |
363A00000X | Clinical Laboratory | Laboratory directors and diagnostic labs manage test performance and reporting |
261QM0800X | Phlebotomy | Personnel performing blood collection in outpatient or hospital settings |
Related Diagnoses
| ICD-10 Code | Description | Clinical Relevance |
|---|---|---|
C18.9 | Malignant neoplasm of colon, unspecified | Common primary diagnosis for which postoperative MRD monitoring with 0340U may be used |
C34.90 | Malignant neoplasm of unspecified part of bronchus or lung | ctDNA MRD assays can be applied in lung cancer surveillance when tumor-informed panels are available |
C50.919 | Malignant neoplasm of unspecified site of unspecified female breast | Breast cancer patients may have tumor-informed ctDNA MRD testing for recurrence surveillance |
C61 | Malignant neoplasm of prostate | Prostate cancer may utilize personalized ctDNA assays in select surveillance contexts |
C80.1 | Malignant neoplasm, unspecified, with metastasis | Used when monitoring for minimal residual disease or molecular recurrence after curative-intent therapy |
Related CPT Codes
| CPT Code | Description | Relationship to This Procedure |
|---|---|---|
81445 | Targeted genomic sequence analysis panel, 5-50 genes | Often precedes 0340U as tumor NGS to identify patient-specific somatic variants used to design the personalized ctDNA assay |
81225 | KRAS gene analysis | Example of tumor genotyping that may be part of the initial molecular profile informing assay design |
36415 | Collection of venous blood by venipuncture | Performed to obtain the plasma specimen used for 0340U testing |
88342 | Immunohistochemistry or special stains (molecular pathology adjunct) | May be part of initial tumor workup that complements genomic profiling prior to assay design |
0000U | Proprietary or PLA placeholder example (not actual) | Data not available in the input. |