Local Coverage Determination (LCD)

MolDX: Breast Cancer Assay: Prosigna®

L36811

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Proposed LCD
Proposed LCDs are works in progress that are available on the Medicare Coverage Database site for public review. Proposed LCDs are not necessarily a reflection of the current policies or practices of the contractor.

Document Note

Note History

Contractor Information

LCD Information

Document Information

Source LCD ID
N/A
LCD ID
L36811
Original ICD-9 LCD ID
Not Applicable
LCD Title
MolDX: Breast Cancer Assay: Prosigna®
Proposed LCD in Comment Period
N/A
Source Proposed LCD
DL36811
Original Effective Date
For services performed on or after 02/16/2017
Revision Effective Date
For services performed on or after 03/30/2023
Revision Ending Date
N/A
Retirement Date
N/A
Notice Period Start Date
01/01/2017
Notice Period End Date
02/15/2017
AMA CPT / ADA CDT / AHA NUBC Copyright Statement

CPT codes, descriptions and other data only are copyright 2023 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein.

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Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association (AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any product or publication; creating any modified or derivative work of the UB‐04 Manual and/or codes and descriptions; and/or making any commercial use of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital Association. The American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products and services are not endorsed by the AHA or any of its affiliates.

Issue

Issue Description

Review completed 03/02/2023 with no change in coverage.

Issue - Explanation of Change Between Proposed LCD and Final LCD

CMS National Coverage Policy

Title XVIII of the Social Security Act (SSA), §1862(a)(1)(A), states that no Medicare payment shall be made for items or services that “are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.”

42 Code of Federal Regulations (CFR) §410.32 Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests and §80.1.1 Certification Changes

Coverage Guidance

Coverage Indications, Limitations, and/or Medical Necessity

This policy provides limited coverage of the Prosigna® Breast Cancer Gene Signature Assay to patients that meet the following criteria consistent with the United States (U.S.) Food and Drug Administration (FDA) indications for use:

  • Post-menopausal female either
    • ER+, lymph node-negative, stage I or II breast cancer; or
    • ER+, lymph node-positive (1-3 positive nodes), stage II breast cancer.

Claims for Prosigna® testing will be denied when testing does not meet all of the above criteria.

Background
Women with early breast cancer and up to 3 locally positive lymph nodes whose tumor is estrogen-receptor positive will usually receive anti-hormonal therapy such as tamoxifen or aromatase inhibitors. U.S. (NCCN) and international (St. Gallen) guidelines predicate the decision for adjuvant chemotherapy on the size and grade of the breast cancer and other factors including genomic assays that provide additional information on risk of recurrence (Hernandez-Ava, et al., 2013). According to a 2014 review, “Prognostic factors provide an indication of whether a patient needs subsequent therapy.” (Paoletti & Hayes, 2014). Similarly, another 2014 review article states, “Efforts should be focused on reducing chemotherapy in patients unlikely to benefit.” (Rampurwala, et al., 2014). Accordingly, Medicare has covered breast cancer gene signature prognostic/predictive tests since 2006.

The PAM50 breast cancer gene signature test was developed in the late 1990s and initial studies showed a strong correlation with breast cancer recurrence and with complete pathologic response to neoadjuvant chemotherapy (Parker, et al., 2009). While test results are reported on a scale of 1-100 as a Risk of Recurrence (ROR) score, the underlying algorithm is also able to classify cases into the luminal A and B, Her2neu, and triple-negative subtype classifications.

The Nanostring nCounter® nucleic acid analysis system replicates the PAM50 algorithm, as an FDA cleared kit, the Prosigna® Breast Cancer Gene Signature Assay (FDA, 2013). The Prosigna® package insert was most recently updated in January 2015 (FDA, 2015) reflecting additional studies (Sestak, et al., 2014). Notably, the Prosigna® platform and the original PAM50 platform have a 0.997 correlation (Dowsett, et al., 2013).

For the FDA, the Prosigna® test was validated in a large population of post-menopausal, estrogen-receptor positive women based on 1,017 cases of the TransATAC study (Dowsett, et al., 2013). The study showed a strong correlation with long-term breast cancer recurrence and added substantial additional prognostic information over a clinical treatment score based on standard clinical variables. This study was replicated in an independent population, also on the Prosigna® test, using 1,620 samples from the ABCSG8 trial (Gnant, 2014). A separate analysis of these trials validated prediction of distant recurrence in years 5-10 after initial diagnosis (Sestak, et al., 2014) and has been incorporated in the FDA labeling (FDA, 2015). The Prosigna® test is issued as separate reports, consistent with FDA review and labeling, for node-negative and node-positive (1-3 node) populations. Analytic performance, precision, reproducibility, and analysis of the clinical validations are provided in the FDA labeling (FDA, 2013; FDA, 2015).

Clinical utility of this breast cancer gene signature has also been assessed. The study of Martin, et al. (2015) showed a 20% decision impact on decisions for or against adjuvant chemotherapy in an all-comers population of 200 new cases of incident breast cancer, when Prosigna® test information became available after all other clinical information had been considered. The net rates of selecting adjuvant chemotherapy for low, intermediate, and high risk cases was similar to that observed in a meta-analysis of Oncotype DX decision data (Carlson & Roth, 2013). Additional support for the use of these test results in treatment decisions comes from Parker, et al. (2009), in which there was a strong association with neoadjuvant chemotherapy response. Low-scoring cases have a very low chance of complete pathological response to neoadjuvant chemotherapy, while high-scoring cases approach a 50% chance of complete pathological response. The same findings have been observed for other breast cancer gene signatures based on prognostic algorithms (Chang, et al., 2008).

Summary of Evidence

NA

Analysis of Evidence (Rationale for Determination)

NA

Proposed Process Information

Synopsis of Changes
Changes Fields Changed
N/A
Associated Information
Sources of Information
Bibliography
Open Meetings
Meeting Date Meeting States Meeting Information
N/A
Contractor Advisory Committee (CAC) Meetings
Meeting Date Meeting States Meeting Information
N/A
MAC Meeting Information URLs
N/A
Proposed LCD Posting Date
Comment Period Start Date
Comment Period End Date
Reason for Proposed LCD
Requestor Information
This request was MAC initiated.
Requestor Name Requestor Letter
N/A
Contact for Comments on Proposed LCD

Coding Information

Bill Type Codes

Code Description
N/A

Revenue Codes

Code Description
N/A

CPT/HCPCS Codes

Group 1

Group 1 Paragraph

N/A

Group 1 Codes

N/A

N/A

ICD-10-CM Codes that Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

ICD-10-CM Codes that DO NOT Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

Additional ICD-10 Information

General Information

Associated Information

Documentation Requirements
The patient's medical record must contain documentation that fully supports the medical necessity for services included within this LCD. (See “Coverage Indications, Limitations, and/or Medical Necessity") This documentation includes, but is not limited to, relevant medical history, physical examination, and results of pertinent diagnostic tests or procedures.

Documentation supporting the medical necessity should be legible, maintained in the patient's medical record, and must be made available to the MAC upon request.

Sources of Information

N/A

Bibliography
  1. Carlson JJ, Roth JA. The impact of Oncotype DX breast cancer assay in clinical practice: A systematic review and meta-analysis. Breast Cancer Res Treat. 2013;141:13-22.
  2. Chang JC, Makris A, Gutierrez MC, et al. Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat. 2008;108:233-240.
  3. Dowsett M, Sestak I, Lopez-Knowles E, et al. Comparison of PAM50 Risk of Recurrence score with Oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol. 2013;31(22):2783-2790.
  4. FDA (2013). 510(k) Summary: K130010. Prosigna Breast Cancer Prognostic Gene Signature Assay. Accessed February 16, 2023.
  5. FDA (2015) Package Insert: Prosigna Breast Cancer Prognostic Gene Signature Assay. Version 04, 18 pages. link: https://www.prosigna.com/resources/ Accessed February 16, 2023.
  6. Gnant M, Filipits M, Greil R, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: Using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol. 2013;25:339-345.
  7. Hernandez-Aya LF, Gonzalez-Angulo AM. Adjuvant systemic therapies in breast cancer. Surg Clin North Am. 2013; 93(2):473–491.
  8. Martin M, Gonzalez-Rivera M, Morales S, et al. Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer. Curr Med Res Opin. 2015;31(6):1129-1137.
  9. Paoletti C, Hayes DF. Molecular testing in breast cancer. Ann Rev Med. 2014;65:95-110.
  10. Parker JS, Mullins M, Cheang MCU, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160-1167.
  11. Rampurwala M, Rocque GB, Burkard ME. Update on adjuvant chemotherapy for early breast cancer. Breast Cancer: Basic and Clinical Research. 2014;8:125-134.
  12. Sestak I, Cuzick J, Dowsett M, et al. Prediction of late distant recurrence after 5 years of endocrine treatment: A combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and Arimidex, Tamozigen alone or in combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol. 2014;33:916-922.

Revision History Information

Revision History Date Revision History Number Revision History Explanation Reasons for Change
03/30/2023 R5

Posted 03/30/2023: Review completed 03/02/2023 with no change in coverage. Updates made to citations in Bibliography to reflect correct AMA formatting. Updated accession dates.

  • Other (Review)
04/22/2021 R4

04/22/21 Under LCD Title added a registered mark to Prosigna®. Under CMS National Coverage Policy added regulation CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests and §80.1.1 Certification Changes. Under Bibliography changes were made to citations to reflect AMA citation guidelines. Prosigna® was inserted throughout the LCD where applicable. Formatting, punctuation and typographical errors were corrected throughout the LCD. Acronyms were defined and inserted where appropriate throughout the LCD. Reviewed on 03/04/2021.

  • Provider Education/Guidance
11/01/2019 R3

Change Request 10901 Local Coverage Determinations (LCDs): it will no longer be appropriate to include Current Procedure Terminology (CPT)/Health Care Procedure Coding System (HCPCS) codes or International Classification of Diseases Tenth Revision-Clinical Modification (ICD-10-CM) codes in the LCDs. All CPT/HCPCS, ICD-10 codes, and Billing and Coding Guidelines have been removed from this LCD and placed in the Billing and Coding Article related to this LCD. Consistent with Change Request 10901, if any language from IOMs and/or regulations was present in the LCD, it has been removed and the applicable manual/regulation has been referenced. Removed regulations regarding billing and coding from the CMS National Coverage policy section and were placed in the billing and coding article. Review completed 11/22/2019.

  • Other (Annual Review)
12/01/2018 R2

12/01/2018-Annual review completed 11/06/2018.

  • Other (Annual Review)
01/01/2018 R1

01/01/2018: Code update. Added 81520 & removed 0008M.  Annual Review completed 12/06/2017. At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To CPT/HCPCS Code Changes
  • Other (Annual Review)
N/A

Associated Documents

Attachments
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Related National Coverage Documents
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Public Versions
Updated On Effective Dates Status
03/22/2023 03/30/2023 - N/A Currently in Effect You are here
04/13/2021 04/22/2021 - 03/29/2023 Superseded View
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

Keywords

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