Summary & Overview
CPT 0422U: Guardant360Response™ ctDNA NGS Assay for Treatment Response
CPT code 0422U designates Guardant Health Inc.'s Guardant360Response™, a proprietary next-generation sequencing (NGS) circulating tumor DNA (ctDNA) assay that quantifies change from a prior baseline test to evaluate response to anticancer therapy. As a PLA code, 0422U is uniquely tied to a single manufacturer's test and is used when the laboratory reports a quantitative comparison with the baseline test 0326U, including specific alterations when present. Nationally, PLA codes like 0422U matter because they standardize billing for novel, lab-specific molecular diagnostics that inform treatment response decisions and precision oncology pathways.
Key payers addressed include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the code's clinical purpose, expected service setting, and payer landscape. The publication summarizes benchmark considerations, coding context for PLA tests, and clinical utility in monitoring solid-organ neoplasm response to systemic anticancer therapies. Data limitations: information on modifiers beyond commonly used modifiers, associated taxonomies, and specific ICD-10 pairings are not available in the input.
Billing Code Overview
CPT code 0422U is a Proprietary Laboratory Analyses (PLA) code specific to Guardant Health Inc.'s Guardant360Response™ test. The assay is a next-generation sequencing (NGS) targeted panel that analyzes cell-free circulating tumor DNA (ctDNA) from a blood specimen to evaluate genes associated with solid-organ neoplasms. The code applies only to this single, manufacturer-specific test and reports a quantitative change from an earlier baseline test, 0326U, using an algorithmic comparison to assess patient response to anticancer therapy.
Service type: Laboratory — Proprietary NGS-based circulating tumor DNA (ctDNA) response assay
Typical site of service: Clinical laboratory or outpatient blood-draw setting (phlebotomy) with specimen sent to the performing laboratory for NGS analysis
Clinical & Coding Specifications
Clinical Context
A typical patient is a 62-year-old with metastatic non-small cell lung cancer (NSCLC) receiving targeted therapy. The patient had an initial Guardant360Response™ baseline blood test (0326U) at treatment start. After two to three treatment cycles or at clinical suspicion of progression, the oncology team orders Guardant360Response™ (0422U) to evaluate quantitative changes in circulating tumor DNA (ctDNA) compared with the baseline. A peripheral blood sample is drawn in the outpatient oncology clinic or an ambulatory phlebotomy site and sent to the performing laboratory. The laboratory performs next-generation sequencing (NGS) targeted analysis of cell-free DNA, applies the proprietary algorithm to compare to baseline results, and issues a report quantifying change in tumor fraction and listing specific genomic alterations if present. The oncology clinician reviews the report to inform assessment of treatment response, consider imaging correlation, and decide on therapy continuation, modification, or additional diagnostic evaluation.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
00 | Unspecified modifier (used by some carriers as default) | Rarely used; follow payer guidance if a neutral modifier is required by claim form. |
22 | Increased procedural services | Use when the laboratory documents a substantially greater level of work or complexity beyond typical assay processing, and payer allows modifier 22 for lab services.
52 | Reduced services | Use when a partial or limited testing is performed compared with the standard Guardant360Response™ test (e.g., insufficient sample leading to limited panel results).
53 | Discontinued procedure | Use if testing was started but not completed and documentation supports a medically necessary discontinuation (e.g., specimen compromised during processing).
26 | Professional component | Use if billing for the physician professional component separately from the laboratory when applicable (note: PLA codes are typically billed by the performing lab; use only if applicable and supported).
TC | Technical component | Use when billing only the laboratory technical component and a separate professional interpretation is not billed.
90 | Reference (outside) laboratory | Use when the servicing laboratory performs the test for another billing laboratory or provider that then bills the payer.
91 | Repeat clinical diagnostic laboratory test | Use when the same test is repeated on the same day to confirm a prior result, if payer permits.
59 | Distinct procedural service | Use only if another unrelated service is provided on the same day that is not normally billed together; documentation must justify distinctness.
XE | Separate encounter | Use when services are distinct because they occurred during separate encounters on the same date of service.
| Taxonomy Code | Specialty | Notes |
|---|---|---|
208000000X | Hematology & Oncology | Medical oncology and hematology specialists order and interpret ctDNA response testing. |
207Q00000X | Medical Oncology | Oncology clinicians manage systemic therapy and use results for response assessment.
207K00000X | Surgical Oncology | May order testing when systemic therapy response is evaluated around surgical planning.
363L00000X | Laboratory Geneticists | Laboratory directors and molecular pathology specialists oversee NGS assay validation and interpretation.
207LR0400X | Hematopathology | Pathologists with molecular expertise may provide clinical interpretation and reporting.
Related Diagnoses
| ICD-10 Code | Description | Clinical Relevance |
|---|---|---|
C34.90 | Malignant neoplasm of unspecified part of bronchus or lung, unspecified | Common primary diagnosis for which ctDNA response monitoring with Guardant360Response™ may be used. |
C50.919 | Malignant neoplasm of unspecified site of unspecified female breast | Breast cancer patients with metastatic disease may have ctDNA monitored for treatment response.
C18.9 | Malignant neoplasm of colon, unspecified | Colorectal cancers with metastatic disease commonly use ctDNA assays for response and minimal residual disease assessment.
C79.9 | Secondary malignant neoplasm of unspecified site | Represents metastatic disease where serial ctDNA testing informs systemic therapy response.
C80.1 | Malignant (primary) neoplasm, unspecified | Used for cases of known malignancy under systemic therapy when specific primary is not otherwise coded but response monitoring is indicated.
Related CPT Codes
| CPT Code | Description | Relationship to This Procedure |
|---|---|---|
0326U | Guardant360® baseline targeted NGS assay for ctDNA (baseline comparator) | Baseline assay required for comparison: 0422U reports quantitative change versus this baseline test. |
0042U | Proprietary laboratory test (example PLA code format) | Data not directly provided for other PLA codes; related PLA tests may be ordered for complementary genomic profiling when diagnostic workup expands.
81479 | Unlisted molecular pathology procedure | May be used for custom or additional molecular analyses not captured by existing PLA codes when clinically indicated.
81025 | Urine pregnancy test, single-step method | Performed pre-treatment when required for therapy safety (example ancillary service in workflow).
36415 | Collection of venous blood by venipuncture | Phlebotomy code used for blood sample collection before sending specimen to the laboratory performing 0422U.