| Coverage Policy Manual | |
| Policy #: | 2023031 |
| Category: | Laboratory |
| Initiated: | June 2023 |
| Last Review: | November 2024 |
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| Laboratory Testing Investigational Services | |
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| Description: |
There are numerous commercially available genetic and molecular diagnostic, prognostic, and therapeutic tests for individuals with certain diseases or asymptomatic individuals with future risk. This review relates to genetic and molecular diagnostic tests not addressed in a separate review. If a separate evidence review exists, then conclusions reached there supersede conclusions here. The main criterion for inclusion in this review is the limited evidence on the clinical utility for the test. As these tests do not have clinical utility, the evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
This policy addresses laboratory services considered to be investigational. These tests are often available on a clinical basis before the required and necessary evidence base to support clinical validity and utility is established. Because these tests are often proprietary, there may be no independent test evaluation data available in the early stages to support the laboratory's claims regarding test performance and utility. While studies using these tests may generate information that may help elucidate the biologic mechanisms of disease and eventually help design treatments, the tests listed in this policy are currently in a developmental phase, with limited evidence of clinical utility for diagnosis, prognosis, or risk assessment.
Regulatory Status
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.
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Policy/ Coverage: |
Effective September 2023, coverage policies 2015008 (Genetic Test: Miscellaneous Genetic and Molecular Diagnostic Tests), 2016019 (Short Tandem Repeat Analysis for Specimen Provenance Testing [know error® system]), and 2023031 ( Laboratory Testing Investigational Services) were combined into one policy (2023031). Policies 2015008 and 2016019 are now archived.
Effective November 2023
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
All tests listed in this policy do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, all tests listed in this policy are considered investigational. Investigational services are considered specific contract exclusions in most member benefit certificates of coverage.
Gastroenterology (irritable bowel syndrome [IBS]), immunoassay for anti-CdtB and anti-vinculin antibodies does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, gastroenterology (irritable bowel syndrome [IBS]), immunoassay for anti-CdtB and anti-vinculin antibodies is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Genetic Testing for CCND1/IGH (t(11;14)) translocation analysis does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, genetic testing for CCND1/IGH (t(11;14)) translocation analysis is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Gene expression profiling for cutaneous melanoma (81529) by real time RT PCR does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, gene expression profiling for cutaneous melanoma (81529) by real time RT PCR is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective September 2023 through October 2023
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
All tests listed in this policy do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, all tests listed in this policy are considered investigational. Investigational services are considered specific contract exclusions in most member benefit certificates of coverage.
Gastroenterology (irritable bowel syndrome [IBS]), immunoassay for anti-CdtB and anti-vinculin antibodies does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, gastroenterology (irritable bowel syndrome [IBS]), immunoassay for anti-CdtB and anti-vinculin antibodies is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Genetic Testing for CCND1/IGH (t(11;14)) translocation analysis does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, genetic testing for CCND1/IGH (t(11;14)) translocation analysis is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Gene expression profiling for cutaneous melanoma (81529) by real time RT PCR does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, gene expression profiling for cutaneous melanoma (81529) by real time RT PCR is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective June 2023 – August 2023
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
All tests listed in this policy do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, all tests listed in this policy are considered investigational. Investigational services are considered specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
This review was created in June 2023 with a search of the PubMed database. The most recent literature update was performed through June 1, 2023.
Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.
The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.
Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.
Diagnostic Testing
Multiple Conditions
Single nucleotide variants (SNVs) are the most common type of genetic variation, and each SNV represents a difference in a single nucleotide in the DNA sequence. Most commonly, SNVs are found in the DNA between genes and can act as biologic markers of genes and disease association. When SNVs occur within a gene or a gene regulatory region, they can play a more direct role in disease by affecting the gene's function. Single nucleotide variants may predict an individual's response to certain drugs, susceptibility to environmental factors, and the risk of developing certain diseases.
DNA specimen provenance assays can be used to confirm that tissue specimens are correctly matched to the patient of origin. Specimen provenance errors may occur in up to 1% to 2% of pathology tissue specimens and have serious negative implications for patient care if the error is not corrected (Pfeifer, 2011; Beauvais, 2013). Analysis of DNA microsatellites from tissue specimens can be performed by analyzing long tandem repeats (LTR) and comparing the LTRs of the tissue specimen with LTRs from a patient sample.
The DNA Methylation Pathway Profile (Mosaic Diagnostics) analyzes SNVs associated with certain biochemical processes, including methionine metabolism, detoxification, hormone imbalances, and vitamin D function. Intended uses for the test include clarification of a diagnosis suggested by other testing and as an indication for supplements and diet modifications.
No full-length, peer-reviewed studies of the DNA Methylation Pathway Profile were identified.
The know error system (Strand Diagnostics) compares the LTRs of tissue samples with LTRs from a buccal swab of the patient. The intended use of the test is to confirm tissue of origin and avoid specimen provenance errors due to switching of patient samples, mislabeling, or sample contamination.
Evidence for the clinical validity of the know error Specimen Provenance Assay is lacking. There is some evidence on the application of short tandem repeat testing for specimen provenance assays in general, but these data are not specific to the know error test (Pfeifer, 2012).
There is a lack of published evidence on the use of the know error test to confirm the tissue of origin. Studies are needed that compare the use of know error with standard laboratory quality measures and that demonstrate a reduction in specimen provenance errors associated with the use of know error.
Celiac Disease
Previously called sprue, celiac sprue, gluten-sensitive enteropathy, gluten intolerance, nontropical sprue, or idiopathic steatorrhea, celiac disease is an immune-based reaction to gluten (water-insoluble proteins in wheat, barley, rye) that primarily affects the small intestine. Celiac disease occurs almost exclusively in patients who carry at least 1 human leukocyte antigen DQ2 or DQ8; the negative predictive value of having neither allele exceeds 98% (Pallav, 2014). Serum antibodies to tissue transglutaminase, endomysium, and deamidated gliadin peptide support a diagnosis of celiac disease, but diagnostic confirmation requires duodenal biopsy taken when patients are on a gluten-containing diet (Ludvigsson, 2013).
Celiac PLUS (Prometheus Laboratories) is a panel of 2 genetic and 5 serologic markers associated with celiac disease. Per the manufacturer, Celiac PLUS is a diagnostic test that also stratifies the future risk of celiac disease (Prometheus Laboratories, 2023). Genetic markers (human leukocyte antigen DQ2 and DQ8) are considered predictive of the risk of developing celiac disease; serologic markers(immunoglobulin A [IgA] anti-tissue transglutaminase antibody, IgA anti-endomysial antibodies, IgA anti-deamidated gliadin peptide antibodies, IgG anti-deamidated gliadin peptide, and total IgA) are considered diagnostic for celiac disease (Pietzak, 2009). Celiac PLUS is intended for patients at risk for the disease (e.g., with an affected first-degree relative) or with symptoms suggestive of the disease.
Celiac PLUS tests for genetic and serologic factors known to be associated with celiac disease. All 7 test components are included in an evidence-based diagnostic algorithm developed by the American College of Gastroenterology (Rubio-Tapia, 2013). However, algorithmic testing is individualized according to the baseline risk of disease and is done sequentially, rather than simultaneously as in Celiac PLUS.
No studies of the combined serologic and genetic Celiac PLUS test were identified. Information about clinical validity of obtaining several serologic and genetic tests at once (i.e., Celiac PLUS) is lacking; improved sensitivity and reduced specificity may be expected.
No studies examining the clinical validity or clinical utility of Celiac PLUS were identified. Factors that support a chain of evidence for prognostic or diagnostic utility are lacking.
Irritable Bowel Syndrome
Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder that affects 10% to 20% of the general population in the U.S. and worldwide. Symptoms include abdominal pain and/or bloating associated with disordered bowel habit (constipation, diarrhea, or both). Pathophysiology is poorly understood but may be related to chronic low-grade mucosal inflammation and disturbances in GI flora (Ford, 2014). Recommended treatments include dietary restriction and pharmacologic symptom control (NICE, 2017; McKenzie, 2012; Weinberg, 2014). As living microorganisms that promote health when administered to a host in therapeutic doses, probiotics are being investigated as a treatment for IBS (Hill, 2014). Several systematic reviews of randomized controlled trials (RCTs) have found evidence to support efficacy, but results from recent RCTs have been mixed (Ford, 2014; Trinkley, 2011; Hungin, 2013; Ortiz-Lucas, 2013; Whelan, 2011; Stevenson, 2014; Shavakhi, 2014; Ludidi, 2014; Rogha, 2014; Urgesi, 2014; Sisson, 2014). This discrepancy may be due in part to the differential effects of different probiotic strains and doses.
The GI Effects Comprehensive Stool Profile (Genova Diagnostics) is a multianalyte stool assay (Genova Diagnostics, 2023). The test uses polymerase chain reaction (PCR) to quantify 26 commensal gut bacteria and standard biochemical and culture methods to measure levels of other stool components (e.g., lipids, fecal occult blood) and potential pathogens (ova and parasites, opportunistic bacteria, yeast). The test is purported to optimize management of gut health and to differentiate IBS from inflammatory bowel disease (IBD).
No studies were identified that assessed the accuracy of the GI Effects fecal panel for diagnosing IBS or for documenting "gut health," a concept that may be difficult to define given large interindividual variability in gut flora (Hanaway, 2006).
Evidence for the clinical validity and utility of the GI Effects Comprehensive Stool Profile is lacking. Because probiotics are not currently a standard treatment of IBS, the impact of test results on disease management is uncertain; i.e., a chain of evidence for clinical utility of the test cannot be established.
Inflammatory Bowel Disease
Inflammatory bowel disease is an autoimmune condition characterized by inflammation of the bowel wall and has clinical symptoms of abdominal pain, diarrhea, and associated symptoms. Crohn disease (CD) and ulcerative colitis are the 2 main entities under the category of IBD. The diagnosis is typically made by endoscopy or colonoscopy with biopsy and histologic analysis. This requires a semi-invasive procedure; as a result, a blood test to diagnose IBD could avoid the need for the procedures.
IBD sgi Diagnostic (Prometheus Laboratories) is a panel of 17 serologic (n=8), genetic (n=4), and inflammatory (n=5) biomarkers. A proprietary algorithm produces an IBD score; results are reported as consistent with IBD (consistent with ulcerative colitis, consistent with CD, or inconclusive for ulcerative colitisvs. CD) or not consistent with IBD. The test is intended for use in patients with clinical suspicion of IBD.
The IBD sgi Diagnostic product monograph includes an extensive bibliography that documents associations of the 18 component markers, individually and in combination, with ulcerative colitis and/or Crohn disease (CD) (Prometheus Laboratories, 2023).
In a review of the monograph, Shirts et al observed that serologic tests for ASCA-IgA, ASCA-IgG, and atypical perinuclear anti-neutrophil cytoplasmic antibody are standard of care in the diagnostic workup of IBD, although not all investigators include these tests in recommended diagnostic strategies (Shirts, 2012; Conrad, 2014; Laass, 2014; Ordas, 2012; Kornbluth, 2010; Baumgart, 2012; Lichtenstein, 2009). These 3 markers are included in the 18-marker panel. Based on a 2006 meta-analysis of 60 studies (N=11,608), Reese et al (2006) reported that pooled sensitivity and specificity of the 3-test panel were 63% and 93%, respectively, for diagnosing IBD (Reese, 2006). Because the product monograph did not compare the 18-marker panel with the 3-marker panel, incremental improvement in diagnosis with the 18-marker panel is unknown. Shirts et al calculated an area under the curve for the 3-marker panel of 0.899.
Published evidence supports associations of each marker in the 18-marker panel, alone and in combination, with IBD diagnosis. Based on manufacturer data, the accuracy for IBD diagnosis of the 18-marker panel exceeds that of each component marker, but the relevant comparison with a panel of 3 markers that has good discrimination for IBD was not included; subsequent analysis has suggested that the panels may perform similarly. Performance characteristics for the 18-marker panel to distinguish ulcerative colitis from CD were not provided.
No studies examining the clinical utility of IBD sgi Diagnostic were identified. Although manufacturer data supported the clinical validity of the test for diagnosing IBD, this evidence is insufficient to support a chain of evidence for clinical utility. For distinguishing ulcerative colitis from CD, clinical validity has not been established; therefore, a chain of evidence for clinical utility for this purpose cannot be established.
Prognostic Testing
Crohn Disease
Recent studies have identified serologic and genetic correlates of aggressive CD that is characterized by fistula formation, fibro stenosis, and the need for surgical intervention (Targan, 2005; Ippoliti, 2010; Abreu, 2002). Prometheus has developed a blood test that aims to identify patients with CD who are likely to experience an aggressive disease course.
Crohn's Prognostic (Prometheus Laboratories) is a panel of 6 serologic (n=3) and genetic (n=3) biomarkers. Limited information about the test is available on the manufacturer's website.
No studies of the 6-marker Crohn's Prognostic test were identified.
Direct and indirect evidence for clinical utility of the Crohn's Prognostic test to identify individuals likely to have an aggressive disease course are currently lacking.
Laboratory Testing Investigational Services
Clinical Context and Test Purpose
The purpose of various commercially available genetic and molecular diagnostic, prognostic, and therapeutic tests in patients relevant indications is to inform a clinical management decision that improves the net health outcome.
No formal evidence review was conducted. To sufficiently evaluate clinical utility, the following PICO characteristics must be well-defined.
Populations
The relevant population of interest are individuals with various indications for diagnostic, prognostic, therapeutic, or future risk assessment testing.
To sufficiently evaluate clinical utility, the intended use population should be clearly defined, including disease state, stage or severity, prior treatment, and symptomatic status. For genetic diseases, details regarding inheritance and penetrance provide valuable context.
Interventions
This review addresses the following tests:
Polygenic risk scores: These tests may estimate an individual's genetic risk of a certain disease and are calculated by adding the number of genetic risk variants, weighted by their effect size. These scores can be combined with physical and social environment risk factors for better risk stratification.
MicroGenDx (MicroGen Diagnostics): This test uses quantitative polymerase chain reaction and next-generation sequencing (NGS) to diagnose various infections. Proposed uses include the evaluation of culture-negative infections, evaluation of patients not responding to current treatments, or in cases where other causes have been ruled out (MicroGen Diagnostics, 2023).
Apolipoprotein L1 (APOL1) Renal Risk Variant Genotyping (Quest Diagnostics): This test utilizes bi-directional Sanger sequencing analysis to detect genetic variants in the APOL1 gene associated with increased risk for renal disease. APOL1 testing may be applied in the kidney transplant setting to predict long-term renal outcomes for donors and recipients (Quest Diagnostics, 2023).
Thyroid GuidePx (Protean Biodiagnostics): This test utilizes NGS to provide a molecular sub-classification of papillary thyroid cancer with prognostic risk assessment. Patient stratification into low, intermediate, and high-risk groups may influence the clinical management of papillary thyroid cancer, particularly in the identification of individuals with a very low risk of recurrence to guide more conservative treatment (Protean Biodiagnostics, 2023).
To sufficiently evaluate clinical utility, the characteristics of the test should be well-defined including thresholds, cutoffs, or classifications used for categorization. The intended use of the test should be clearly stated, including its position in the clinical pathway. Use of the test to replace an existing test or testing pathway (replacement), use before an existing test or testing pathway (triage), or use after an existing test or testing pathway (add-on) should be clearly specified.
Comparators
The clinical practice alternative to which the test is being compared should be clearly stated, including any applicable reference standards and any known disadvantages of the comparator that the test under evaluation aims to overcome.
Outcomes
The general outcomes of interest are symptoms, quality of life, medication use, change in disease status, and morbidity and mortality. Follow-up duration may be informed by the natural history of the disease.
Health outcomes measure length of life, quality of life, and the ability to function and occur as a consequence of the interventions taken as a result of the test. Clinical management decisions and physiologic measures that are not validated surrogates are not health outcomes. The beneficial outcomes resulting from a true test result and the harmful outcomes resulting from a false test result should be clearly stated. Clinical management recommendations for a test result that is discordant with another test applied in the clinical pathway should also be defined.
Clinically Useful
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.
The studies using the tests listed in this policy are currently in a developmental phase, with limited evidence of clinical utility for diagnosis, prognosis, or risk assessment. The lack of demonstrated clinical utility of these tests is based on the following factors: (1) there is no or extremely limited published data addressing the test; and/or (2) it is unclear where in the clinical pathway the test fits (replacement, triage, add-on); and/or (3) it is unclear how the test leads to changes in management that would improve health outcomes and/or avoiding existing burdensome and invasive testing; and/or (4) thresholds for decision making have not been established; (5) and/or the outcome from the test result does not change in a way we find value in, relative to the outcomes(s) obtained without the test.
With the clinical utility not established, evidence review of clinical validity was not performed.
Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from randomized controlled trials.
Chain of Evidence
Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility.
Supplemental Information
The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.
Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in 'Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.
American Urological Association et al
In 2019, the American Urological Association (AUA) published joint guidelines with the Canadian Urological Association (CUA) and the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) on the management of recurrent uncomplicated urinary tract infections in women (Anger, 2019). Regarding the use of polymerase chain reaction (PCR) and next-generation sequencing (NGS) techniques for the identification of bacterial species, the guideline states that "more evidence is needed before these technologies become incorporated into the guideline, as there is concern that adoption of this technology in the evaluation of lower urinary tract symptoms may lead to over treatment with antibiotics."
In 2016, the AUA published joint guidelines with the Society of Urologic Oncology on the diagnosis and treatment of non-muscle invasive bladder cancer (Chang, 2016). For use of urinary biomarkers after diagnosis, the guidelines state: "a clinician should not use urinary biomarkers in place of cystoscopic evaluation" (Strong Recommendation; Evidence Strength: Grade B); that "in a patient with a history of low-risk cancer and a normal cystoscopy, a clinician should not routinely use a urinary biomarker or cytology during surveillance (Expert Opinion); and that "in a patient with NMIBC, a clinician may use biomarkers to assess response to intravesical BCG (UroVysion FISH) and adjudicate equivocal cytology (UroVysion FISH and ImmunoCyt) (Expert Opinion)."
National Comprehensive Cancer Network
NCCN-Bladder Cancer v.3.2023 states urine biomarkers may be considered during surveillance of high-risk non-muscle invasive bladder cancer; yet, due to unclear clinical utility states that such is a 2B recommendation (NCCN, 2023).
The NCCN (v.2.2023) guidelines for colon cancer state that it has "not been established if molecular markers are useful in treatment determination (predictive markers) and prognosis" (NCCN, 2023).
National Human Genome Research Institute et al
In 2021, the National Human Genome Research Institute's ClinGen Complex Disease Working Group updated the Genetic Risk Prediction (GRIPS) Reporting Statement in collaboration with the Polygenic Score (PGS) Catalog (Wand, 2021).
American College of Gastroenterology
Celiac Disease
In 2023, the American College of Gastroenterology published a clinical practice update for the diagnosis and management of celiac disease (Singh, 2023). A recommendation for genetic testing using a multigene panel test (e.g., Celiac PLUS) was not included.
Inflammatory Bowel Disease
In 2018, the American College of Gastroenterology practice guidelines on Crohn disease state that genetic and routine serologic testing is not indicated to establish the diagnosis of Crohn's disease (Lichtenstein, 2018).
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed below.
NCT05276466a Assessment of Urinary Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS) Technology in the Evaluation and Management of Females With Chronic Bladder Pain and Cystitis-like Symptoms Planned Enrollment: 100 Completion Date: Dec 2023
NCT05287438a Next Generation Sequencing Versus Traditional Cultures for Clinically Infected Penile Implants: Impact of Culture Identification on Outcomes Planned Enrollment: 40 Completion Date: Oct 2024
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2024. No new literature was identified that would prompt a change in the coverage statement.
Additional 2024 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
NCCN clinical practice guidelines on prostate cancer (v.4.2024) state that "there are advanced risk stratification tools (i.e., gene expression biomarkers, AI digital pathology) that have been variably demonstrated to independently improve risk stratification beyond NCCN or CAPRA risk stratification" and that "these tools are recommended to be used when they have the potential ability to change disease management. These tools should not be ordered reflexively. The most common treatment decisions in localized prostate cancer to use these tests include the use and/or intensity of active surveillance versus radical therapy, [radiotherapy](RT) versus RT + short-term (ST)-[androgen deprivation therapy](ADT), and RT + ST-ADT versus long-term (LT)-ADT. The most common treatment decisions in biochemically recurrent prostate cancer post-RP to use these tests include secondary RT versus secondary RT + ADT. These tools are not recommended for patients with very-low-risk prostate cancer. There are an extensive number of these tools created with substantial variability in quality of reporting and model design, endpoint selection, and quality and caliber of validation. It is recommended to use models that have high-quality and robust validation, ideally with high-quality, long-term clinical trial data, which usually comes from randomized trials and across multiple clinical trials" (NCCN, 2024).,For the ArteraAI Prostate test 2A recommendation, continuous scores may be used to provide more accurate risk stratification to inform shared decision-making; however, NCCN notes that "specific score cut points have not been published to date for specific treatment decisions." Predictive biomarker testing with ArteraAI in individuals with intermediate-risk prostate cancer can help to identify patients with a more favorable prognostic risk who "may consider the use of RT alone" without ST-ADT.
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| References: |
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