BlueAdvantage Administrators of Arkansas
Coverage Policy#: 970
Category: Laboratory
Initiated: November 2013
Last Review: February 05, 2026
Last Revision: February 05, 2026
BlueAdvantage National Accounts
Coverage Policy for Participants and Beneficiaries enrolled in Walmart Associates' Health and Welfare Medical Plan
(Developed by BlueAdvantage Administrators and Adopted by the Walmart Plan as Plan Coverage Criteria)

Genetic Test: Gene Expression Profiling and Protein Biomarkers for Prostate Cancer Management

Description:
Gene expression profile analysis and protein biomarkers have been proposed as a means to risk-stratify patients with prostate cancer to guide treatment decisions. These tests are intended to be used either on prostate needle biopsy tissue to guide management decisions for active surveillance or therapeutic intervention, to guide radiotherapy use after radical prostatectomy (RP), or to guide medication selection after progression in metastatic castration-resistant prostate cancer.
 
PROSTATE CANCER
Prostate cancer is the second most common noncutaneous cancer diagnosed among men in the United States. Autopsy studies in the era before the availability of prostate-specific antigen (PSA) screening have identified incidental cancerous foci in 30% of men 50 years of age, with incidence reaching 75% at age 80 years (Dal’Era et al, 2008).
   
Localized prostate cancers may appear very similar clinically at diagnosis (Bangma, 2007). However, they often exhibit diverse risk of progression that may not be captured by accepted clinical risk categories (e.g., D’Amico criteria) or prognostic tools that are based on clinical findings, including PSA titers, Gleason grade, or tumor stage (Johansson, 2004; Ploussard, 2011; Hamden, 2008; Brimo, 2013; Eylert, 2012). In studies of conservative management, the risk of localized disease progression based on prostate cancer-specific survival rates at 10 years may range from 15% (8, 9) to 20% (Thompson, 2013) to perhaps 27% at 20-year follow-up (Albertsen, 2005). Among elderly men (70 years or more) with this type of low-risk disease, comorbidities typically supervene as a cause of death; these men will die with prostate cancer present, rather than from the cancer.  Other very similar-appearing low-risk tumors may progress unexpectedly rapidly, quickly disseminating and becoming incurable.   
 
Risk Stratification in Newly Diagnosed Disease
In the United States, most prostate cancers are clinically localized at diagnosis due in part to the widespread use of PSA testing. Clinicopathologic characteristics are used to stratify patients by risk based on the extent of the primary tumor (T category), nearby lymph node involvement (N category), metastasis (M category), PSA level and Gleason score. The National Comprehensive Cancer Network (2017) and American Urological Association (2017) risk categories for clinically localized prostate cancer are similar, derived from the D’Amico criteria and broadly include low-, intermediate-, or high-risk as follows as well as subcategories within these groups:
    • Low: T1-T2a and Gleason score < 6 grade group 1 and PSA level <10 ng/mL;
    • Intermediate: T2b-T2c or Gleason score 3+4=7/Gleason grade group 2 or Gleason score 4=3=7/Gleason grade group 3 or PSA level 10-20 ng/mL;
    • High: T3a or Gleason score 8/Gleason grade group 4 or Gleason score 9-10/Gleason grade group 5 or PSA level >20 ng/mL.
 
Risk stratification is combined with patient age, life expectancy, and treatment preferences to make initial therapy decisions.
 
Principles of Risk Stratification and Biomarkers for Prostate Cancer
Predictive biomarkers and risk stratification methods are the primary tools within clinical practice that may aid in the treatment of individuals with localized and advanced prostate cancer. The NCCN uses multiple categories and subgroupings to capture prognostic risk and provide a method for risk-stratification to allow standardized treatment recommendations for individuals with localized and advanced prostate cancer (13. These tools are separated by type and category:
 
Type:
    • "Standard Tools: These include clinical and/or pathologic variables routinely collected to assign a patient to an NCCN categoryand/or subgroup. Examples include TNM stage, Grade Group, PSA, and metastatic volume of disease."
    • "Clinical and Pathologic Tools: These include clinical and/or pathologic tools that are generally derived from standard tools.Examples include multivariable models or nomograms, histologic variants, and PSA kinetics."
    • "Advanced Tools: These involve an additional test above what is collected to assign an NCCN category or subgroup. These mayinclude, but are not limited to, germline or somatic tests, gene expression tests, digital histopathology-based tests, imaging, andcirculating markers."
Category:
    • "Prognostic: Discriminates the risk of developing an oncologic endpoint (eg, distant metastasis). The relative benefit of atreatment (ie, the treatment effect or hazard ratio) is generally similar across a prognostic spectrum, although the absolute benefitof an intervention may vary by risk (ie, number needed to treat [NNT])."
        • "Prognostic biomarkers independently discriminate and are associated with a clinically meaningful endpoint above andbeyond standard tools relevant to that disease setting that ultimately helps guide a therapeutic decision."
    • "Predictive: Discriminates a difference in the relative benefit of a specific treatment for an oncologic endpoint."
        • "Predictive biomarkers have been demonstrated to measure a biomarker-treatment interaction that ultimately helps guidea therapeutic decision in the context of a randomized trial, specifically randomizing the treatment of interest."
 
Monitoring After Prostatectomy
All normal prostate tissue and tumor tissue is theoretically removed during radical prostatectomy (RP), so the serum level of PSA should be undetectable following RP. Detectable PSA post-RP indicates residual prostate tissue and presumably persistent or recurrent disease. PSA is serially measured following RP to detect early disease recurrence. The National Comprehensive Cancer Network (2017) recommends monitoring serum PSA every 6 to 12 months for the first 5 years and annually thereafter. Many recurrences following RP can be successfully treated. The American Urological Association has recommended a biochemical recurrence be defined as a serum PSA of 0.2 ng/mL or higher, which is confirmed by a second determination with a PSA level of 0.2 ng/mL or higher (Thompson et al, 2013).
 
Castration-Resistant Prostate Cancer
Androgen deprivation therapy (ADT) is generally the initial treatment for patients with advanced prostate cancer. ADT can produce tumor response and improve quality of life but most patients will eventually progress on ADT. Disease that progresses while the patient is on ADT is referred to as castration-resistant prostate cancer. After progression, continued ADT is generally used in conjunction with other treatments. Androgen pathways are important in the progression of castration-resistant prostate cancer. Several drugs have been developed that either inhibit enzymes involved in androgen production or inhibit the androgen receptor, such as abiraterone and enzalutamide. Taxane chemotherapy with docetaxel or cabazitaxel may also be used after progression. Immunotherapy (sipuleucel-T) or radium 223 are options for select men.
 
Decision Framework for Evaluating Prostate Cancer Biomarkers
Simon et al Framework
Many studies have investigated individual biomarkers or combinations of biomarkers associated with prostate cancer outcomes. Determining which studies constitute sufficient evidence that the test or biomarker is likely to be clinically useful depends on attributes of the test such as its performance and the quality of the study generating the results. Simon et al (2009) have described a framework to evaluate prognostic biomarker evidence. Study designs, such as prospective clinical trials or previously conducted clinical trials with archived tumor samples, constitute stronger evidence than studies with less planned and systematic patient recruitment and data collection. Randomized trials allow the determination of treatment-biomarker interactions that may be clinically important. In some clinical scenarios, demonstration of a treatment-biomarker interaction is not critical, because the decision to withhold chemotherapy in a low-risk group (to avoid chemotherapy-related morbidity) does not require the presence of a biomarker-treatment interaction. The study must generate an absolute estimate of outcomes in the patient group of interest that would result in a change in management (eg, withholding of chemotherapy), and the study must have sufficient precision (narrow confidence intervals). Results of the same test across studies should show the consistency of results and more than 1 study demonstrating the desired result should be available. Simon et al (2009) have proposed that at least 2 Simon et al (2009) category B studies showing results consistent with clinical utility are necessary to demonstrate adequate evidence of a biomarker. Simon et al (2009) also proposed that while "further confirmation in a separate trial of the results gained from a category A prospective trial is always welcome, compelling results from such a trial would be considered definitive and no other validating trial would be required."
Policy/
Coverage:
Effective February 01, 2026
 
The use of molecular oncologic testing of prostate cancer to guide management in biopsy-proven, untreated, localized adenocarcinoma of the prostate (no clinical evidence of metastasis or lymph node involvement) and a life expectancy of > 10 years may be considered medically necessary and is covered for the following conditions:
 
A_Results of testing will inform decision-making for active surveillance versus definitive therapy for very low-risk, low-risk, or favorable intermediate risk absent evidence the individual is not a candidate for active surveillance or definitive therapy. Genomic Prostate Score [(0047U) GPS previously known as Oncotype DX GPS], Prolaris® (Biopsy Prostate) Cancer Prognostic test (81541), or Decipher Prostate Biopsy Genomic Classifier (81542) is covered as a single use test [NCCN v4.2024];
 
OR
 
B_Results of testing will inform decision-making for active surveillance versus definitive therapy for unfavorable intermediate-risk or high-risk absent evidence the individual is not a candidate for active surveillance or definitive therapy. Prolaris® (Biopsy Prostate) Cancer Prognostic test (81541) or Decipher Prostate Biopsy Genomic Classifier (81542) is covered as a single use test [NCCN v4.2024];
 
OR
 
C_Results of single testing from Decipher Prostate RP (Radical Prostatectomy) Genomic Classifier (81542) will inform use of adjuvant treatment following radical prostatectomy when one or more of the following conditions exist [NCCN v4.2024]:
 
                • PT2 with positive margins,
                • Any evidence of pT3 disease,
                • Rising PSA (above nadir).
 
Policy Guidelines:
 
Very Low-Risk Prostate Cancer: Clinical/pathological features must include all of the following: PSA is less than 10, Grade Group 1, less than 3 biopsy cores positive with less than or equal to 50% cancer in each core and non-palpable disease (T1c), and PSA Density <0.15ng/ml/g. (NCCN Prostate Cancer, v4.2024).
 
Low-Risk Prostate Cancer: Clinical/pathological features must include all of the following, but cancer does not qualify for very low-risk: PSA is less than 10, Grade Group 1, and T1-T2a disease (NCCN Prostate Cancer, v4.2023)
 
Favorable Intermediate-Risk Prostate Cancer: Clinical/pathological features must include all of the following: No high or very high-risk group features, Grade Group 1 or 2, less than 50% of biopsy cores are positive (e.g., < 6 of 12 cores) and has one intermediate risk factor (T2b-T2c, PSA 10-20) (NCCN Prostate Cancer, v4.2024).
 
Unfavorable Intermediate-Risk Prostate Cancer: Clinical/pathological features must include: No high- or very high-risk group features and one or more of the following: Grade Group 3, = of 50% biopsy cores are positive (e.g., = 6 of 12 cores), and either 2 or 3 intermediate risk factors (T2b-T2c disease, Grade Group 2 or 3, PSA 10-20) (NCCN Prostate Cancer, v4.2023).
 
High-Risk Prostate Cancer: Clinical/pathological features must include all of the following: No very high-risk features and exactly one of the following high-risk features: T3a OR Grade Group 4/5 OR PSA > 20 (NCCN Prostate Cancer, v4.2023).
 
Very High-Risk Prostate Cancer: Clinical/pathological features have at least one of the following: 2 or 3 features of High-Risk Prostate Cancer, Primary Gleason pattern 5, T3b-T4 disease or greater than 4 cores with Grade Group 4 or 5 (NCCN Prostate Cancer, v4.2024).
 
 
The use of any of the above cited molecular panels for testing not meeting the above criteria is considered investigational.
 
The use of any molecular oncologic test for prostate cancer management other than stated as covered above is considered investigational.
 
The use of multimodal artificial intelligence (MMAI) (e.g., ArteraAI Prostate Test, e.g., 0037U) to guide management of prostate cancer is considered investigational in all situations.
 
Investigational services are Plan exclusions.
 
Rationale:
This evidence review has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through July 13, 2025.
 
Analytic validity is the technical accuracy of a test in detecting a mutation that is present or in excluding a mutation that is absent.
 
Clinical validity reflects the diagnostic performance of a test (sensitivity, specificity, positive and negative predictive values) in detecting clinical disease.
 
Clinical utility reflects how the results of a diagnostic test will be used to change management of the patient and whether these changes in management lead to clinically important improvements in health outcomes.
 
 
SUMMARY OF EVIDENCE
 
Initial Management Decision: Active Surveillance vs Therapeutic Intervention
For individuals who have clinically localized untreated prostate cancer who receive Prolaris, the evidence includes retrospective cohort studies of clinical validity using archived samples in patients of mixed risk categories. The relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. For the low-risk group, the ProtecT trial showed 99% 10-year disease-specific survival in mostly low-risk patients receiving active surveillance. The low mortality rate estimated with tight precision makes it unlikely that a test intended to identify a subgroup of low-risk men with a net benefit from immediate treatment instead of active surveillance would find such a group. For the intermediate-risk group, the evidence of improved clinical validity or prognostic accuracy for prostate cancer death using Prolaris Cell Cycle Progression score in patients managed conservatively after a needle biopsy has shown some improvement in areas under the receiver operating characteristic curve over clinicopathologic risk stratification tools.
 
For individuals who have clinically localized untreated prostate cancer who receive Oncotype DX Prostate, the evidence includes case-cohort and retrospective cohort studies of clinical validity using archived samples in patients of mixed risk categories, and a decision-curve analysis examining indirect evidence of clinical utility. The relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. Evidence for clinical validity and potential clinical utility of Oncotype DX Prostate in patients with clinically localized prostate cancer derives from a study predicting adverse pathology after RP. The validity of using tumor pathology as a surrogate for the risk of progression and cancer-specific death is unclear. It is also unclear whether results from an RP population can be generalized to an active surveillance population.
 
For individuals who have clinically localized untreated prostate cancer who receive Decipher Biopsy, the evidence includes retrospective cohort studies of clinical validity using archived samples in intermediate-risk patients and no studies of clinical utility. The relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. For intermediate-risk men, a test designed to identify men who can receive active surveillance instead of RP or RT would need to show very high NPV for disease-specific mortality at ten years and improvement in prediction compared with existing tools used to select such men. Clinical validity studies of Decipher Biopsy reported prostate cancer metastases at five years but did not report survival outcomes.
 
For individuals who have clinically localized untreated prostate cancer who receive the ProMark protein biomarker test, the evidence includes a retrospective cohort study of clinical validity using archived samples and no studies of clinical utility. The relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. Current evidence does not support improved outcomes with ProMark given that only a single clinical validity study is available.
 
For individuals who have clinically localized untreated prostate cancer who receive ArteraAI Prostate Test, the evidence includes 1meta-analysis and 5 retrospective analyses on archived samples from randomized clinical trials on prostate cancer patients of mixed risk categories to assess clinical validity and utility. Relevant outcomes include overall survival (OS), disease-specific survival, quality of life (QOL), and treatment-related morbidity. Evidence for clinical validity and potential clinical utility of ArteraAI Prostate Test in patients with clinically localized prostate cancer derives from a handful of studies comparing relevant outcomes against comparators like National Comprehensive Cancer Network (NCCN) and standard clinicopathologic risk-stratification tools. Multimodal artificial intelligence (MMAI) algorithms, that form the foundation of ArteraAI, have shown they can outperform comparators at prognosticating 10-year outcomes of interest (OS, distant metastasis [DM], biochemical failure [BF], and prostate cancer-specific survival [PCSS]). Additionally, MMAI was able to demonstrate it is predictive for ST-ADT and can determine if prostate cancer patients would have a better net health outcome on radiotherapy (RT) alone or RT plus short-term androgen deprivation therapy (ST-ADT). Limitations of these studies are synonymous with retrospective analysis, including but not limited to, clinical heterogeneity of study populations, variability in data recording, and different conditions under which measurements occurred, etc. No study reported management changes made in response to ArteraAI Prostate Test results, but current NCCN management algorithms recommend MMAI testing with ArteraAI for prostate cancer patients with NCCN intermediate-risk scores to indicate patients that should undergo ST-ADT regardless of RT dose or type. Moreover, NCCN notes that MMAI testing with ArteraAI may provide more accurate risk stratification to enable better management of cancer patients, however, it still remains unclear on how this could be used in clinical practice as specific MMAI cutoff values have not been published.
 
Management Decision After RP
For individuals who have localized prostate cancer treated with RP who receive Prolaris, the evidence includes retrospective cohort studies of clinical validity using archived samples. The relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. Evidence of improved clinical validity or prognostic accuracy for prostate cancer death using the Prolaris Cell Cycle Progression score in patients after prostatectomy has shown some improvement in areas under the receiver operating characteristic curve over clinicopathologic risk stratification tools.
 
For individuals who have localized prostate cancer who are treated with RP and who receive the Decipher prostate cancer classifier, the evidence includes a study of analytic validity, prospective and retrospective studies of clinical validity using overlapping archived samples, decision-curve analyses examining indirect evidence of clinical utility, and prospective decision-impact studies without pathology or clinical outcomes. The relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. The clinical validity of the Decipher genomic classifier has been evaluated in samples of patients with high-risk prostate cancer undergoing different interventions following RP. Studies reported some incremental improvement in discrimination. However, it is unclear whether there is consistently improved reclassification-particularly to higher risk categories-or whether the test could be used to predict which men will benefit from radiotherapy.
 
For individuals who have localized prostate cancer treated with RP who receive ArteraAI Prostate Test, the evidence includes 2retrospective cohort studies of clinical validity using archived samples. Relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. ArteraAI proved to be prognostic for RP-specific endpoints of BCR and adverse pathology (AP) given the statistically significant association. Disease-specific survival outcomes were reported in both studies and the evidence of clinical validity and prognostic accuracy for MMAI scores via ArteraAI testing in patients after RP demonstrated statistically improved prostate cancer specific mortality (PCSM) and OS when compared to standard clinicopathologic risk stratification tools. Limitations of these studies are synonymous with retrospective analysis, including but not limited to, clinical heterogeneity of study populations, variability in data recording, and different conditions under which measurements occurred, etc. No study reported management changes made in response to ArteraAI Prostate Test results. Overall, ArteraAI Prostate Test is validated for disease-specific outcomes for prostate cancer patients who underwent RP and can provide additional prognostic information that may guide postoperative management, but further studies are needed to determine if MMAI can be used to decide specific treatment regimens that improve health outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
 
Management Decision in Castration-Resistant Prostate Cancer
For individuals who have mCRPC who receive the Oncotype DX AR-V7 Nuclear Detect, the evidence includes one prospective cohort study, one retrospective cohort study of clinical validity using archived samples, and no studies of clinical utility. The relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. Current evidence does not support improved outcomes with Oncotype DX AR-V7 Nuclear Detect, given that only two clinical validity studies meeting inclusion criteria were available. The evidence is insufficient to determine the effects of the technology on health outcomes.
 
Management Decision in Castration-Sensitive Prostate Cancer
For individuals who have metastatic castration-sensitive prostate cancer (mCSPC) who receive ArteraAI Prostate Test, the evidence includes 2 retrospective cohort studies of clinical validity using archived samples. Relevant outcomes include OS, disease-specific survival, QOL, and treatment-related morbidity. MMAI was able to estimate treatment effects and determine that MMAI high-risk mCRPC patients would derive benefit from metastasis-directed therapy (MDT) when compared to observation. Limitations of these studies are synonymous with retrospective analysis, including but not limited to, clinical heterogeneity of study populations, variability in data recording, and different conditions under which measurements occurred, etc. No study reported management changes made in response to ArteraAI Prostate Test results. Overall, ArteraAI Prostate Test is prognostic for mCSPC patients and has the potential to guide treatment management, but further studies are needed to determine if MMAI can be used to decide specific treatment regimens that improve net health outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
 
ONGOING AND UNPUBLISHED CLINICAL TRIALS
A search of online site ClinicalTrials.gov registry identified several currently unpublished trials that might influence this policy.
 
PRACTICE GUIDELINES AND POSITION STATEMENTS
 
American Society of Clinical Onclology (ASCO)
In 2020, the American Society of Clinical Onclology (ASCO) published a guideline on molecular biomarkers in localized prostate cancer (Eggener et al, 2020). The guidelines state, "Currently, there are no strong data or expert guidelines to support active surveillance in otherwise healthy men with Grade Group 3 or higher cancer; therefore, we would consider the use of genomic biomarkers only in situations in which the assay result, when considered as a whole with routine clinical factors, is likely to affect a physician’s recommendation or a patient’s choice for surveillance versus treatment, but they should not be used routinely."
 
Specific recommendations included the following:
 
Molecular biomarkers to identify patients with prostate cancer who are most likely to benefit from active surveillance:
    • Recommendation 1.1. Commercially available molecular biomarkers (i.e. Oncotype Dx Prostate, Prolaris, Decipher, and ProMark) may be offered in situations in which the assay result, when considered as a whole with routine clinical factors, is likely to affect management. Routine ordering of molecular biomarkers is not recommended (Type: Evidence based; Evidence quality: Intermediate; Strength of recommendation: Moderate).
    • Recommendation 1.2. Any additional molecular biomarkers evaluated do not have sufficient data to be clinically actionable or are not commercially available and thus should not be offered (Type: Evidence based; Evidence quality: Insufficient; Strength of recommendation: Moderate).
Molecular biomarkers to diagnose clinically significant prostate cancer:
    • Recommendation 2.1. Commercially available molecular biomarkers (i.e. Oncotype Dx Prostate, Prolaris, Decipher, and ProMark) may be offered in situations in which the assay result, when considered as a whole with routine clinical factors, is likely to affect management. Routine ordering of molecular biomarkers is not recommended (Type: Evidence based; Evidence quality: Intermediate; Recommendation: Moderate). Recommendation
    • 2.2. Any additional molecular biomarkers evaluated do not have sufficient data to be clinically actionable or are not commercially available and thus should not be offered (Type: Evidence based; Evidence quality: Insufficient; Strength of recommendation: Moderate).
Molecular biomarkers to guide the decision of post prostatectomy adjuvant versus salvage radiation:
    • Recommendation 3.1. The Expert Panel recommends consideration of a commercially available molecular biomarker (eg, Decipher Genomic Classifier) in situations in which the assay result, when considered as a whole with routine clinical factors, is likely to affect management. In the absence of prospective clinical trial data, routine use of genomic biomarkers in the postprostatectomy setting to determine adjuvant versus salvage radiation or to initiate systemic therapies should not be offered (Type: Evidence based; Evidence quality: Intermediate; Strength of recommendation: Moderate).
    • Recommendation 3.2. Any additional molecular biomarkers evaluated do not have sufficient data to be clinically actionable or are not commercially available and thus should not be offered (Type: Evidence based; Evidence quality: Insufficient; Strength of recommendation: Moderate).
American Urological Association and American Society for Radiation Oncology
The American Urological Association and American Society for Radiation Oncology published guidelines on clinically localized prostate cancer (Eastham et al, 2022).
The guidelines included the following statements on risk assessment:
    1. "Clinicians should use clinical T stage, serum PSA, Grade Group (Gleason score), and tumor volume on biopsy to risk stratify patients with newly diagnosed prostate cancer.(Strong Recommendation; Evidence Level: Grade B)"
    2. "Clinicians may selectively use tissue-based genomic biomarkers when added risk stratification may alter clinical decision-making. (Expert Opinion)"
    3. "Clinicians should not routinely use tissue-based genomic biomarkers for risk stratification or clinical decision-making. (Moderate Recommendation; Evidence Level: Grade B)"
In 2018, the American Urological Association published guidelines for castration-resistant prostate
Cancer (Lowrance et al, 2018). The guidelines do not mention AR-V7 assays.
 
National Comprehensive Cancer Network (NCCN)
The National Comprehensive Cancer Network guidelines for prostate cancer (v.2025) provide a table of tissue-based tests for prostate cancer prognosis.
 
Guidelines are updated frequently; refer to the source document for current recommendations. The most recent guidelines (v.1.2025) include the following recommendations and statements related to risk-stratification and testing for biomarkers:
 
22-gene genomic classifier (GC) (Decipher)
    • "RT alone may be considered for patients with a low GC score and NCCN intermediate-risk disease"
    • "The addition of ST-ADT should be considered for patients with a high GC score given their increased risk of DM and significant benefit of ST-ADT on DM, irrespective of RT dose or brachytherapy boost"
    • "Patients with a GC low-risk score should be counseled that the absolute benefit of LT-ADT over ST-ADT is smaller than forpatients with GC high-risk scores and when accounting for patient age, comorbidities, and patient preferences, it may be reasonable with shared decision-making to use a duration shorter than LT-ADT"
    • "For patients with node-negative disease post-RP planned for early secondary RT (PSA = 0.5 ng/mL) with GC low or intermediate risk, use of RT alone should be considered"
    • "For patients planned for early secondary RT with a GC high-risk tumor, use of secondary RT with ADT is recommended"
ArteraAI Prostate Test
    • Patients with intermediate-risk prostate cancer planning to receive RT, those with biomarker-positive disease, and especially those with unfavorable intermediate-risk disease, should be recommended for the addition of ST-ADT regardless of RT dose or type, notwithstanding contraindications to ADT. Those with biomarker (-) tumors, especially tumors with more favorable prognostic risk, may consider the use of RT alone
    • "Specific MMAI cut points have not been published to date to precisely guide specific treatment decisions. Rather, the test maybe used to provide more accurate risk stratification to enable improved shared decision-making"
The discussion section in the guidelines, which is pending update as of April 2024 include the following statements related to risk stratification:
    • Patients with low or favorable intermediate-risk disease and life expectancy greater than or equal to 10 years may consider the use of Decipher, Oncotype DX Prostate, or Prolaris during initial risk stratification.
    • Patients with unfavorable intermediate- and high-risk disease and life expectancy greater than or equal to 10 years may consider the use of Decipher or Prolaris.
    • Decipher may be considered to inform adjuvant treatment if adverse features are found after radical prostatectomy and during workup for radical prostatectomy PSA persistence or recurrence (NCCN category 2A; Simon et al [2019] category 2B)
The panel also stated that "the use of AR-V7 tests in circulating tumor cells can be considered to help guide selection of therapy in the post-abiraterone/enzalutamide metastatic castration-resistant prostate cancer setting."
 
Of note, in the April 2024 version of the NCCN guideline, the following footnotes were noted to be removed, but the related discussion sections are still pending update:
    • "Decipher molecular assay should be considered if not previously performed to inform adjuvant treatment if adverse features are found post- RP."
    • "Consider AR-V7 testing to help guide selection of therapy."
National Institute for Health and Care Excellence
In 2019, the National Institute for Health and Care Excellence updated its guidance on the diagnosis and management of prostate cancer.  The guidance did not address gene expression profile testing.
 
U.S. Preventive Services Task Force Recommendations
Not applicable.
 
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 (CLIA). Prolaris® (Myriad Genetics), Oncotype DX® Prostate and Oncotype DX AR-V7 Nuclear Detect (Genomic Health), Decipher gene expression profiling test (DecipherCorp), and
the ProMark™ protein biomarker test (Metamark Genetics), and Artera® Prostate Test are available under the auspices ofthe CLIA. Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date, the U.S.Food and Drug Administration (FDA) has chosen not to require any regulatory review of these tests.
 
In November 2015, the FDA’s Office of Public Health Strategy and Analysis published a document on public health evidence for FDA oversight of LDTs. The FDA argued that many tests need more FDA oversight than the regulatory requirements of the CLIA. The CLIA standards relate to laboratory operations but do not address inaccuracies or unreliability of specific tests. Prolaris is among the 20 case studies in the document cited as needing FDA oversight. The report asserted that patients are potentially receiving inappropriate prostate cancer care because there is no evidence that results from the test meaningfully improve clinical outcomes.
 
 
Current References
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CPT/HCPCS:
0011MOncology, prostate cancer, mRNA expression assay of 12 genes (10 content and 2 housekeeping), RT PCR test utilizing blood plasma and urine, algorithms to predict high grade prostate cancer risk
0047UOncology (prostate), mRNA, gene expression profiling by real time RT PCR of 17 genes (12 content and 5 housekeeping), utilizing formalin fixed paraffin embedded tissue, algorithm reported as a risk score
0376UOncology (prostate cancer), image analysis of at least 128 histologic features and clinical factors, prognostic algorithm determining the risk of distant metastases, and prostate cancer-specific mortality, includes predictive algorithm to androgen deprivation-therapy response, if appropriate
81541Oncology (prostate), mRNA gene expression profiling by real time RT PCR of 46 genes (31 content and 15 housekeeping), utilizing formalin fixed paraffin embedded tissue, algorithm reported as a disease specific mortality risk score
81542Oncology (prostate), mRNA, microarray gene expression profiling of 22 content genes, utilizing formalin fixed paraffin embedded tissue, algorithm reported as metastasis risk score
81599Unlisted multianalyte assay with algorithmic analysis
ICD9:
ICD10:
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