Retired Local Coverage Determination (LCD)

MolDX: ConfirmMDx Epigenetic Molecular Assay

L35632

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Retired

Contractor Information

LCD Information

Document Information

LCD ID
L35632
LCD Title
MolDX: ConfirmMDx Epigenetic Molecular Assay
Proposed LCD in Comment Period
N/A
Source Proposed LCD
DL35632
Original Effective Date
For services performed on or after 10/01/2015
Revision Effective Date
For services performed on or after 12/17/2020
Revision Ending Date
07/03/2022
Retirement Date
07/03/2022
Notice Period Start Date
07/19/2018
Notice Period End Date
09/02/2018
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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

Palmetto GBA will provide limited coverage for the ConfirmMDx epigenetic assay for prostate cancer (MDxHealth, Irvine, CA) to reduce unnecessary repeat prostate biopsies. Palmetto 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.  Palmetto 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
N/A
Sources of Information
N/A
Bibliography
  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.
  17. Partin A W, et al. Clinical Validation of an Epigenetic Assay to Predict Negative Histopathological Results in Repeat Prostate Biopsies, J Urol 2014, Volume 192, Issue 4 , 1081 - 1087.
  18. Van Neste L, et al. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies. The Prostate 76.12 2016: 1078-1087.

 

Revision History Information

Revision History DateRevision History NumberRevision History ExplanationReasons for Change
07/03/2022 R14

This LCD is being retired because the information in this policy has been incorporated within the MolDX: Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer L38985 LCD. 

  • LCD Being Retired
12/17/2020 R13

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

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
10/31/2019 R12

This LCD is being revised in order to adhere to CMS requirements per Chapter 13, Section 13.5.1 of the Program Integrity Manual, to remove all coding from LCDs. There has been no change in coverage with this LCD revision.Regulations regarding billing and coding were removed from the CMS National Coverage Policy section of this LCD and placed in the related Billing and Coding: MolDX: ConfirmMDx Epigenetic Molecular Assay A56955 article.

  • Provider Education/Guidance
08/29/2019 R11

All coding located in the Coding Information section has been moved into the related Billing and Coding: MolDX: ConfirmMDx Epigenetic Molecular Assay A56955 article and removed from the LCD.

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
09/03/2018 R10

This LCD version was created as a result of DL35632 being released to a Final LCD.

  • Other
02/26/2018 R9 The Jurisdiction "J" Part B Contracts for Alabama (10112), Georgia (10212) and Tennessee (10312) are now being serviced by Palmetto GBA. The notice period for this LCD begins on 12/14/17 and ends on 02/25/18. Effective 02/26/18, these three contract numbers are being added to this LCD. No coverage, coding or other substantive changes (beyond the addition of the 3 Part B contract numbers) have been completed in this revision.
  • Change in Affiliated Contract Numbers
01/01/2018 R8

Removed 81479 from CPT/HCPCS codes.

  • Revisions Due To CPT/HCPCS Code Changes
01/01/2018 R7

2018 Annual CPT/HCPCS Updates: Added 81551 to CPT/HCPCS Codes.

  • Revisions Due To CPT/HCPCS Code Changes
07/20/2017 R6

Updated a typographical error in the reference numbering.

 

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 Added R97.20 to Group 1 under ICD-10 Codes that Support Medical Necessity.
  • Revisions Due To ICD-10-CM Code Changes
10/01/2016 R4 ICD-10 Code Changes.

R97.2 was deleted from Group 1

N40.0 descriptor was changed in Group 1 from Enlarged prostate without lower urinary tract symptoms to Benign prostatic hyperplasia without lower urinary

N40.1 descriptor was changed in Group 1 from Enlarged prostate with lower urinary tract symptoms to Benign prostatic hyperplasia with lower urinary tr
  • Revisions Due To ICD-10-CM Code Changes
11/27/2015 R3 Add "-CDD" after MolDX in the LCD title to identify policy as Coverage with Data Development
  • Other (Add "-CDD" after MolDX in the LCD title to identify policy as Coverage with Data Development)
10/01/2015 R2 Completed Annual Validation
  • Other (Annual Validation)
10/01/2015 R1 Corrected IOM 100-04, Chapter 23, Section 10 to remove ICD-9 reference.
  • Other (IOM Update)

Associated Documents

Attachments
N/A
Related National Coverage Documents
N/A
Public Versions
Updated On Effective Dates Status
07/03/2022 12/17/2020 - 07/03/2022 Retired You are here
12/10/2020 12/17/2020 - N/A Superseded View
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

Keywords

  • ConfirmMDx

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