Billing Code Overview

CPT code 0539U is a Proprietary Laboratory Analyses (PLA) code that applies exclusively to the PredicineCARE™ Assay from Predicine Inc. This laboratory test analyzes cell–free circulating tumor DNA (ctDNA) from whole–blood samples using next‑generation sequencing (NGS). The assay evaluates 152 genes to detect a range of genomic alterations including single‑nucleotide variants, insertions and deletions, gene rearrangements, copy number alterations, and microsatellite instability, providing information on genetic mutations with potential treatment implications.

Service type: Laboratory — NGS‑based ctDNA genomic profiling

Typical site of service: Clinical laboratory or reference lab; specimen collection in an outpatient clinic or phlebotomy setting

Clinical Context

A 62-year-old patient with a history of metastatic non–small cell lung cancer (NSCLC) presents for evaluation of progressive disease after first-line therapy. The treating oncologist orders the PredicineCARE™ Assay (0539U) to analyze cell-free circulating tumor DNA (ctDNA) from a whole-blood sample using next-generation sequencing. The goal is to identify actionable genomic alterations across 152 genes (including single-nucleotide variants, insertions/deletions, gene rearrangements, copy number alterations, and microsatellite instability) to inform targeted therapy selection or clinical trial eligibility. The clinical workflow includes: blood draw at an outpatient infusion center or ambulatory lab; specimen shipping to the performing laboratory; NGS-based ctDNA analysis and bioinformatics processing; and generation of a molecular report reviewed by the oncologist to guide treatment planning. Typical site of service is an outpatient phlebotomy collection center, oncology clinic, or freestanding laboratory facility. Common payors include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, BUCA plans, and Medicare.

Coding Specifications

| 22 | Increased procedural services | Use when documentation justifies substantially greater effort or complexity associated with test processing or reporting beyond usual test complexity

| 52 | Reduced services | Use if testing was partially performed or limited compared with the full assay (e.g., preanalytic sample compromised resulting in partial analysis)

| 53 | Discontinued procedure | Use when the specimen collection or processing was started but abandoned and the payer requires reporting of an interrupted service

| 59 | Distinct procedural service | Use when reporting separate, unrelated laboratory services from the same patient encounter (apply only if payer accepts modifier with PLA codes)

| 24 | Unrelated evaluation and management service by the same physician during a postoperative period | Use if an unrelated E/M is provided on the same day as ordering/testing and documentation supports unrelated care

| 90 | Reference (outside) laboratory | Use to indicate testing was performed by an outside laboratory when billing relationships require explicit designation

| 91 | Repeat clinical diagnostic laboratory test | Use when the exact same lab test is repeated on the same day for confirmation of results

| RT | Right side (anatomic) | Not typically applicable to blood-based molecular testing but included for payor systems requiring laterality fields

| LT | Left side (anatomic) | Not typically applicable to blood-based molecular testing but included for payor systems requiring laterality fields

| 2084P0800X | Molecular Pathology | Laboratory directors and molecular pathologists overseeing NGS ctDNA assays

| 207K00000X | Medical Oncology | Physicians managing systemic cancer therapy who use ctDNA results for treatment planning

| 261QP2000X | Clinical Laboratory | Clinical laboratory technologists and managers involved in specimen processing and NGS testing

| 207L00000X | Medical Genetics | Medical geneticists involved in interpretation of complex germline vs somatic findings

Related Diagnoses

| C78.00 | Secondary malignant neoplasm of unspecified lung | Used when evaluating metastatic disease origin and molecular profile via ctDNA

| C80.1 | Malignant (primary) neoplasm, unspecified | Applied for advanced cancers when site is not specified but molecular profiling is indicated to guide therapy

| D37.9 | Neoplasm of uncertain behavior of respiratory and intrathoracic organs, unspecified | Occasionally used when malignancy is suspected and molecular testing is part of diagnostic workup

| Z85.118 | Personal history of malignant neoplasm of bronchus and lung | Relevant when monitoring for recurrence through ctDNA surveillance

| Z51.11 | Encounter for antineoplastic chemotherapy | ctDNA testing frequently coordinated with systemic therapy decision points

| R91.8 | Other nonspecific abnormal finding of lung field | Imaging abnormalities may prompt ctDNA testing when tissue biopsy is infeasible

| Z03.89 | Encounter for observation for other suspected diseases and conditions | May be used during diagnostic evaluation when molecular testing is obtained as part of workup

Related CPT Codes

| 99000 | Handling and/or conveyance of specimen for transfer from patient to lab | Used by some facilities for specimen handling logistics when billed separately

| 0001U | Proprietary laboratory analysis code (example PLA) | Other PLA molecular tests that may be ordered concurrently or as alternatives depending on clinical needs

| 81479 | Unlisted molecular pathology procedure | Used when an alternative or custom molecular test is performed that does not have a specific CPT or PLA code

| G0452 | Pharmacogenomic testing for cancer therapy (example HCPCS) | May be performed in parallel in some care pathways to inform chemotherapy or targeted agent selection