Appeal type: unknown
Decision: unknown

 
The rules say that plans must pay for a medical service or item if regular Medicare would pay for it in this case. 
You can find this rule at 42 Code of Federal Regulations (CFR) Section 422.101. 
 
The rules state that this policy describes and clarifies coverage for Lab-Developed Tests (LDTs), Food and 
Drug Administration (FDA)-cleared, and FDA-approved clinical laboratory tests utilizing Next-Generation 
Sequencing (NGS) in cancer as allowable under the National Coverage Determination (NCD) 90.2, under 
section D describing Medicare Administrative Contractor (MAC) discretion for coverage. This policys scope 
is specific for solid tumor testing, and is exclusive of hematologic malignancies, circulating tumor DNA testing 
(ctDNA), and other cancer-related uses of NGS, such as germline testing in/for patients with cancer. 
Summary of Evidence 
NGS testing in solid tumors is becoming a routine component of the diagnostic process; the results can uncover 
the genomic mechanisms of cancer that have predictive, diagnostic, and prognostic utility to the patient and are 
used to better their management. Understanding the mechanisms of disease and targeting treatment based on 
those aberrant processes (i.e., targeted therapies for biomarkers) has improved patient outcomes in many tumor 
types and is the basis of Precision Medicine. Capturing mutations and other relevant genetic/genomic 
information is standard of care for determining clinical care for many tumor types, including the most common, 
such as melanoma, lung, colorectal, and breast carcinoma. NGS adds the ability to capture abundant genomic 
data both efficiently, and relatively cheaply, and its use is showing to improve patient outcomes although 
studies in this regard are ongoing. The established Centers for Medicare & Medicaid Services (CMS) National 
Coverage policy NCD 90.2 confirms these tests to be both reasonable and necessary in Medicare beneficiaries. 
Professional Society Clinical Practice Guidelines 
Guidelines for validating clinical NGS tests for use in cancer have been published in a joint effort by the 
Association for Molecular Pathology and the College of American Pathologists. Guidelines for employing 
bioinformatics pipelines for NGS testing have also been published by these groups, as well as guidelines for 
interpreting somatic variants in these panels (these same groups in collaboration with the American Society of Clinical Oncology).Guidelines from several societies currently suggest or prefer the use of NGS over other 
methods for lung cancer and colorectal cancer. Additionally, societal guidelines recommend genetic testing for 
other tumor types that can be identified by NGS, such as melanoma, thyroid, brain, and ovarian cancers, among 
others. 
Test Description 
NGS is not a specific test, but a sequencing methodology utilized to capture genomic information. Unlike 
Sanger sequencing (the prior standard technology) that typically provides sequence information for a single 
deoxyribonucleic acid (DNA) strand/molecule, NGS allows for massively parallel sequencing of millions of 
DNA molecules concurrently. This allows for capturing many relevant genomic targets simultaneously, usually 
by utilizing capture technologies such as by polymerase chain reaction (PCR) amplification or hybrid capture. 
As such, NGS tests for use in cancer are often comprised of gene panels whose content is either relevant to a 
specific tumor type or condition, or a larger panel of genes that can be used for multiple tumor types. 
NGS tests can vary significantly for many reasons. While NGS defines a broad methodology for massively 
parallel sequencing, different technologies that have different strengths, weaknesses, and technical limitations 
or liabilities are available. The most common sequencing platforms in clinical use today are from Illumina and 
Thermo Fisher. While both sequence by synthesis similar to Sanger sequencing, these platforms utilize 
different chemistries, signal amplification, and detection methods. Gene panels can include only the portions of 
genes that contain the most critical clinically relevant information, or be comprehensive, containing entire 
exonic gene regions (coding regions), introns (non-coding regions), and even sequence ribonucleic acid (RNA) 
for detecting gene fusions. Downstream from the pre-analytic processes mentioned above, the bioinformatics 
used to process and assess the resultant sequencing reads and identify variants/mutations can yield different 
results based on the software used and what variant types of variants the test is attempting to detect. These 
software tools must take the resultant sequencing file (generally starting with the FASTQ format), align all 
possible sequences with a reference genome (BAM/SAM), and identify variants from the reference (typically a 
VCF file). Once such variants are identified, they must be assessed for validity and subsequently for their 
clinical relevance. The types of genomic information reported can vary, as tests can uncover a myriad of 
genomic alterations such as single nucleotide variants (SNVs), Insertions/Deletions (INDELs), Copy Number 
Alterations (CNAs; these can be simply amplifications at a single locus or chromosomal gains and losses), and 
gene fusions/translocations. The resultant information can also be used to calculate additional relevant 
information, such as Tumor Mutation Burden (TMB), or the presence of microsatellite instability (MSI). All of 
these variant classes have demonstrated clinical utility. As such, NGS testing in cancer comprises a large 
heterogeneous group of assays that are substantially different from each other. Additionally, NGS testing is 
highly complex and requires expertise from handling the specimen, to running complex equipment, to 
understanding the required bioinformatics, to interpreting the findings and creating an actionable medical 
report. Two types of tests are considered for coverage, Hot-spot tests and comprehensive genomic profile 
tests (CGP). The definition of these terms, in addition to appropriate coding information is located in Coverage 
Articles associated with this Local Coverage Determination (LCD). These tests can detect any combination of 
the previously described variant types, but in general, Hot-spot tests are limited to SNVs and small INDELs, whereas CGPs can detect those variants in addition to CNAs, larger INDELs, gene fusions/translocations, and 
be used to calculate MSI status and TMB. 
Analytical Validity and Clinical Utility 
Because of the number of variables described above, additional work must be performed to assess if any given 
test is both reasonable and necessary for Medicare beneficiaries and to ensure that Medicare claims are 
properly understood and executed. Molecular Diagnostic Services Program (MolDX

) has instituted a process 
for completing a Technical Assessment (TA) that ensures that tests are appropriate for their indications and are 
properly validated according to published guidelines described above (when applicable). Specifically, in order 
to understand if a test is both reasonable and necessary, it must be delineated if a test has the properly validated 
technology, variant types, gene and variant coverage, and bioinformatics capability to deliver a clinically useful 
result for the Medicare beneficiary, given their diagnosis. Because of the number of variables described above, 
additional work must be performed to assess if any given test is both reasonable and necessary for Medicare 
beneficiaries and to ensure that Medicare claims are properly understood and executed. MolDX has instituted a 
process for completing a Technical Assessment (TA) that ensures that tests are appropriate for their indications 
and are properly validated according to published guidelines described above (when applicable). Specifically, 
in order to understand if a test is both reasonable and necessary, it must be delineated if a test has the properly 
validated technology, variant types, gene and variant coverage, and bioinformatics capability to deliver a 
clinically useful result for the Medicare beneficiary, given their diagnosis. 
Labs seeking coverage for LDTs or FDA-approved tests that are not nationally covered utilizing NGS in cancer 
must submit documentation to allow MolDX to complete a TA. Forms to complete the process are available on 
the MolDX website. Tests that are currently covered by Palmetto GBA are not exempt from this process. Tests 
that are currently covered and have not undergone a TA by MolDX will be non-covered unless complete 
documents to perform a TA are submitted in a timely manner described below. 
Criteria for Coverage 
All the following must be present for coverage eligibility: 
 As per NCD 90.2, this test is reasonable and necessary when: 
o the patient has either: 
 Recurrent cancer 
 Relapsed cancer 
 Refractory cancer 
 Metastatic cancer 
 Advanced cancer (stages III or IV) 
o AND has not been previously tested by the same test for the same genetic content 
o AND is seeking further treatment 
 The test has satisfactorily completed a TA by MolDX for the stated indications of the test 
 The assay performed includes at least the minimum genes and genomic positions required for the 
identification of all FDA-approved therapies with a companion diagnostic biomarker for its intended 
use that can be reasonably detected by the test. Because these genes and variants will change as the literature and drug indications evolve, they are listed separately in an associated Coverage Article, as 
well as in the MolDX TA forms. 
Situations in which Test should not be used or coverage is denied: 
The test in question will be non-covered if: 
 It does not fulfill all the criteria set forth in the NCD 90.2 as stated above 
 Another CGP test was performed on the same tumor specimen (specimen obtained on the same date of 
service) 
 A TA is not completed satisfactorily by MolDX for new tests 
 For tests that are currently covered but a TA submission has not been made, providers must submit 
completed TA materials by February 10
th
, 2020, or coverage will be denied 
Analysis of Evidence (Rationale for Determination) 
Level of Evidence 
Quality: Strong/variable depending on biomarker and specific test 
Strength: Strong/variable depending on biomarker and specific test 
Weight: Strong/variable depending on biomarker and specific test 
Given the abundant literature on genetic and genomic testing in cancer diagnosis and care, this contractor feels 
strongly that NGS methodology for testing is appropriate for use in Medicare beneficiaries. However, given the 
variability for what information tests can provide, additional information must be submitted by providers to 
ensure the contractor A) understands what test is being performed; B) Why it is being performed; C) If the test 
is both necessary and reasonable for cancer care for its intended use. 
You can find this rule at the Medicare Local Coverage Determination (LCD) L38067: MolDX: Next-
Generation Sequencing for Solid Tumors. 
If you want to read these Medicare rules, you can go to this website www.medicareappeal.com. 
 
The Plan contract says that the Plan covers items and services in accordance with Medicare rules.