Local Coverage Determination (LCD)

MolDX: ConfirmMDx Epigenetic Molecular Assay

L36006

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LCD Information

Document Information

LCD ID
L36006
LCD Title
MolDX: ConfirmMDx Epigenetic Molecular Assay
Proposed LCD in Comment Period
N/A
Source Proposed LCD
DL36006
Original Effective Date
For services performed on or after 10/05/2015
Revision Effective Date
For services performed on or after 04/21/2022
Revision Ending Date
N/A
Retirement Date
N/A
Notice Period Start Date
08/20/2015
Notice Period End Date
10/04/2015
AMA CPT / ADA CDT / AHA NUBC Copyright Statement

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Issue

Issue Description

Annual review on policy, no changes made.

CMS National Coverage Policy

Title XVIII of the Social Security Act, §1862(a)(1)(A). Allows coverage and payment for only those services that are considered to be reasonable and necessary.

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

CMS On-Line Manual, Publication 100-02, Medicare Benefit Policy Manual, Chapter 15, §§80.0, 80.1.1, 80.2. Clinical Laboratory services.

Coverage Guidance

Coverage Indications, Limitations, and/or Medical Necessity

CGS Administrators will provide limited coverage for the ConfirmMDx epigenetic assay for prostate cancer (MDxHealth, Irvine, CA) to reduce unnecessary repeat prostate biopsies. CGS Administrators recognizes that evidence for clinical utility for ConfirmMDx in males with previous negative prostate biopsy who are being considered for repeat biopsy is promising with evidence of some clinical utility at the current time. CGS Administrators believes the clinical studies planned will generate sufficient additional data to demonstrate the utility of ConfirmMDx in males with previous negative prostate biopsy who are being considered for repeat biopsy. Continued coverage of ConfirmMDx for males with previous negative prostate biopsy who are being considered for repeat biopsy will be dependent on semi-annual review of interim data, and/or peer-reviewed publications and/or presentations of clinical utility data demonstrating ConfirmMDx for males with previous negative prostate biopsy directs patient management as measured using clinical endpoints in one or more studies.

Summary of Evidence

ConfirmMDx assesses the methylation status of 3 biomarkers (GSTP1, RASSF1, APC) associated with prostate cancer. ConfirmMDx is intended for use in patients with high-risk factors such as elevated/rising prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE), with a negative or non-malignant abnormal histopathology finding (e.g., atypical cell or high grade prostate intraepithelial neoplasia (HGPIN)) in the previous biopsy, and is being considered for repeat biopsy. Several case/control studies in archived biopsy core tissue blocks demonstrated the sensitivity, specificity and high negative predictive value (NPV) of these biomarkers to predict cancer detection in a repeat biopsy procedure. Single biopsy cores, using as little as 20 microns from formalin-fixed, paraffin embedded (FFPE) tissue blocks or sections cut from blocks fixed on glass slides are used in this assay.

The performance of this assay in large, blinded clinical validation studies demonstrated a NPV of 90% for all prostate cancer and 96% for high-grade disease, which is considerably higher than that afforded by standard histopathology review. A mathematically-based budget impact model using the assay in urologic practices to decide upon the need for repeat biopsies reported significant cost and medical resource savings by avoiding unnecessary, invasive biopsies over current standard of care methods. Further logistic regression models using all pertinent risk factors for prostate cancer detection (patient age, serum PSA level, digital rectal exam, histopathological findings on the previous cancer-negative biopsy and the assay) from the clinical validation trial were analyzed to compare various metrics separately and in combination. Assay results and prior histopathology were the strongest predictors of missed cancers and these two measures combined had a higher performance than either alone. Further analysis demonstrated that the assay test results combined with traditional clinical risk factors improved patient risk stratification and significantly outperformed current risk prediction models such as the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC 2.0) and PSA.

The repeat biopsy rate for patients with an initial negative biopsy was reported to be approximately 40% in the Prostate, Lung, Colorectal and Lung (PLCO) screening trial suggesting that a majority of the patients undergoing repeat biopsies did not have cancer detected. A completed field observation study was conducted in 138 patients with negative biopsies and managed by the urologist receiving negative ConfirmMDx for Prostate Cancer assay findings from those patient’s tissues. Only 6 of the 138 patients in that series had received a repeat biopsy yielding a 4.5% repeat biopsy rate.

Analysis of Evidence (Rationale for Determination)

Level of Evidence

Quality of the Evidence: Moderate
Strength of the Evidence: Low
Weight of the Evidence: Low

ConfirmMDx is covered under the following conditions:

  1. Males aged 40 to 85 years old that have undergone a previous cancer-negative prostate biopsy within 24 months and are being considered for a repeat biopsy due to persistent or elevated cancer-risk factors, and
  2. The previous negative prostate biopsy must have collected a minimum of 8 tissue cores (but not have received a saturation biopsy of > 24 tissue cores) and remaining FFPE tissue from all cores is available for testing, and
  3. Minimum tissue volume criteria of 20 microns of prostate biopsy core tissue is available (40 microns preferable), and
  4. Previous biopsy histology does not include a prior diagnosis of prostate cancer or cellular atypia suspicious for cancer (but may include the presence of high-grade prostatic intraepithelial neoplasia (HGPIN), proliferative inflammatory atrophy (PIA), or glandular inflammation), and
  5. Patient is not being managed by active surveillance for low stage prostate cancer, and
  6. Tissue was extracted using standard patterned biopsy core extraction (and not transurethral resection of the prostate (TURP)), and
  7. Patient has not been previously tested by ConfirmMDx from the same biopsy samples or similar molecular test.

General Information

Associated Information
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Sources of Information

References:

  1. Ahmed H, et al. Evidence of heavy methylation in the galectin 3 promoter in early stages of prostate adenocarcinoma: development and validation of a methylated marker for early diagnosis of prostate cancer. Transl Oncol. 2009; Aug 18; 2(3): 146-¬-56.
  2. Aubry W, et al. Budget impact model: epigenetic assay can help avoid unnecessary repeated prostate biopsies and reduce healthcare spending. American Health Drug and Benefits 2013; Jan/Feb; 6(1): 15-¬-24.
  3. Bastian P, et al. Prognostic value of CpG island hypermethylation at PTGS2, RAR-¬-beta, EDNRB, and other gene loci in patients undergoing radical prostatectomy. Eur Uro 2007; Mar; 51(3): 885-¬-74.
  4. Devaney J, et al. The epigenetic promise for prostate cancer diagnosis. Cancer Epidemiol Biomarkers Prev 2011; Jan; 20(1): 148-9.
  5. Gonzales C, et al. AUA/SUNA white paper on the incidence, prevention and treatment of complications related to prostate needle biopsy. AUA White Paper 2012.
  6. Mehorta J, et al. Quantitative, spatial resolution of the epigenetic field effect in prostate cancer. The Prostate 2008; Feb 1; 68(2): 152-60.
  7. Steiner I, et al. Gene promoter methylation and its potential relevance in early prostate cancer diagnosis. Pathobiology 2010; Nov; 77(5): 260-¬-6.
  8. Stewart G, et al. Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies results of the MATLOC study. J Urol 2013; Mar; 189(3): 110-¬-6.
  9. Taneja S et al. AUA/optimal techniques of prostate biopsy and specimen handling. AUA White Paper 2013.
  10. Trock B, et al. Evaluation of GSTP1 and APC methylation as indicators for repeat biopsy in a high-¬-risk cohort of men with negative initial prostate biopsies. BJU Int. 2013; Jul; 110(1): 56–62..
  11. Troyer D, et al. Prostate cancer detected by methylated gene markers in histopathologically cancer-¬-negative tissues from men with subsequent positive biopsies.Cancer Epidemiol Biomarkers Prev 2009; Oct; 18(10): 2717-¬-22.
  12. Trujillo L, et al.Markers of field cancerization: Proposed clinical applications in prostate biopsies.Prostate Cancer 2012; 2012:302894.
  13. Van Neste L, et al. A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection. BMC Urology 2012; Jun 6; 12:16.
  14. Van Neste, et al. The epigenetic promise for prostate cancer diagnosis. The Prostate 2011; Aug 1;72(11): 1248-61.
  15. Wojno KJ et al. Reduced rate of repeated prostate biopsies observed in ConfirmMDx clinical utility field study. Am Health Drug Benefit, 2014; May; 7(3):129-34.
  16. Zon G, et al. Formamide as a denaturant for bisulfite conversion of genomic DNA: Bisulfite sequencing of the GSTPi and RARβ2 genes of 43 formalin-¬fixed paraffin-¬embedded prostate cancer specimens. Anal Biochem 2009; Sept 15; 392(2): 117-¬-25.

 

Bibliography

N/A

Revision History Information

Revision History DateRevision History NumberRevision History ExplanationReasons for Change
04/21/2022 R19

R19

Revision Effective: 04/21/2022

Revision Explanation: Annual review , no changes made.

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.

  • Other (Annual review)
04/22/2021 R18

R18

Revision Effective: 04/22/2021

Revision Explanation: Annual review , no changes made.

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.

  • Other (Annual REview)
12/17/2020 R17

R17

Revision Effective: 12/17/2020

Revision Explanation: Under Summary of Evidence changed Prostate, Lung, Ovarian and Lung to read Prostate, Lung, Colorectal and Ovarian.

10/30/2020: 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.

  • Provider Education/Guidance
11/07/2019 R16

R16

Revision Effective: 08/25/2020

Revision Explanation: Annual review, no changes made.

08/25/2020: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.

  • Other (Annual review)
11/07/2019 R15

R15

Revision Effective: 11/07/2019

Revision Explanation: Removed CDD from the title and the following regulations from the CMS National policy section and placed them in the billing and coding article:

Title XVIII of the Social Security Act, Section 1833(e). This section prohibits Medicare payment for any claim that lacks the necessary information to process the claim; and

Medicare Internet Online Manual Pub. 100-4 (Medicare Claims Processing Manual), Chapter 23 (Section 10) “ICD-9-CM Coding for Diagnostic Tests”.

10/28/2019: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 Code Removal
09/19/2019 R14

R14

Revision Effective: 09/23/2019 Revision Explanation: Annual review, no changes made.

09/23/2019: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.

  • Other (Annual review, no changes made)
09/19/2019 R13

R13

Revision Effective: 09/19/2019 Revision Explanation: Converted policy into new policy template that no longer includes coding section based on CR 10901. For Approval, no changes.

09/13/2019: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 Code Removal
09/19/2019 R12

R12

Revision Effective: 09/19/2019 Revision Explanation: Converted policy into new policy template that no longer includes coding section based on CR 10901.

09/12/2019: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 Code Removal
09/12/2019 R11

R11

Revision Effective: September 12, 2019

Revision Explanation: All coding located in the Coding Information section has been moved into the related Billing and Coding: MolDX: ConfirmMDx Epigenetic Molecular Assay A57031 article and removed from the LCD.

DATE (09/05/2019): 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.

  • Provider Education/Guidance
01/01/2018 R10

R10

Revision Effective: N/A

Revision Explanation: Annual review no changes made.

DATE (08/27/2019): 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.

  • Other (Annual Review )
01/01/2018 R9

R9

Revision Effective: N/A

Revision Explanation: Annual review no changes made.

DATE (08/13/2018): 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.

  • Other (Annual review)
01/01/2018 R8

R8

Revision Effective: 01/01/2018

Revision Explanation: Replaced unlisted code 81479 with new code 81551 during annual HCPCS update.

DATE (12/13/2017): 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
07/20/2017 R7

R7

Revision Effective: N/A

Revision Explanation: Annual review no changes made.

DATE (08/28/2017): 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.


  • Other (annual review)
07/20/2017 R6

R6
Revision Effective: 07/20/2017
Revision Explanation: Corrected typographical error in the reference section fro numbering.

07/24/2017-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.

  • Typographical Error
10/01/2016 R5 R5
Revision Effective: 10/01/2016
Revision Explanation: Added R97.20 to group 1.
  • Revisions Due To ICD-10-CM Code Changes
10/01/2016 R4 R4
Revision Effective: 10/01/2016
Revision Explanation: During annual ICD-10 update R97.2 was deleted.
  • Revisions Due To ICD-10-CM Code Changes
10/05/2015 R3 R3
Revision Effective: N/A
Revision Explanation: Annual review no changes made.
  • Other (Annual Review)
10/05/2015 R2 R2
Revision Effective: 10/05/2015
Revision Explanation: Added -CDD after MolDX in title of policy to distinguish coverage with data development.
  • Other (Added to title name)
10/05/2015 R1 R1
Revision Effective: 10/05/2015
Revision Explanation: Changed MoPath to MolDX.
  • Other (Title Update)

Associated Documents

Attachments
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Related National Coverage Documents
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Public Versions
Updated On Effective Dates Status
04/15/2022 04/21/2022 - N/A Currently in Effect You are here
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

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