MolDX: Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer

Jurisdiction: J5 MAC Part B. States: Iowa, Kansas, Missouri, Nebraska. Type: Active LCD

There are two applications of molecular biomarkers to risk-stratify patients at increased risk for prostate cancer: A non-invasive or minimally invasive test, the results of which are obtained to inform the decision to perform an initial biopsy (pre-biopsy). A test performed to further refine risk when a biopsy has been performed but does not clearly indicate malignancy on histopathologic examination (post-biopsy). Such a test can potentially obviate the need for a repeat biopsy. This contractor provides limited coverage for molecular Deoxyribonucleic acid/ribonucleic acid (DNA/RNA) biomarker tests for the diagnosis of prostate cancer that help differentiate men who may or may not benefit from a prostate biopsy when ALL of the following conditions are met: The patient must not have an established diagnosis of prostate cancer. The beneficiary is a candidate for prostate biopsy or repeat prostate biopsy, according to a consensus guideline [(i.e., National Comprehensive Cancer Network ® (NCCN), American Society of Clinical Oncology ® (ASCO), American Urological Association (AUA)]. a) For men ≤ 75 years of age - Prostate Specific Antigen (PSA) (or adjusted PSA in special populations, i.e., patients taking 5alpha-reductase inhibitors) OR repeat PSA are >3 and b) For men > 75 years of age - PSA (or adjusted PSA in special populations, i.e., patients taking 5-alpha-reductase inhibitors) OR repeat PSA are ≥4 and EXCEPTION: a molecular biomarker test may be performed in men with PSA levels >10 ng/mL who are being considered for repeat biopsy IF appropriate according to consensus guidelines AND according to the following: the specific biomarker test has been validated in men with PSA levels>10 ng/mL AND a Multiparametric MRI (mpMRI) is negative, if performed. The beneficiary has not had a prostate biopsy OR has had a previous negative or non-malignant but abnormal histopathology finding (i.e., atypical small acinar proliferation (ASAP) or high-grade prostatic intraepithelial neoplasia (HGPIN) on prostate biopsy). Patients under consideration for a repeat biopsy have first undergone repeat PSA and/or DRE testing as recommended by consensus guidelines The beneficiary would benefit from treatment of prostate cancer and patient management will be impacted by use of a biomarker in a manner already demonstrated in the peer-reviewed published literature to improve patient outcomes. The medical record supports the medical necessity for the biomarker test. Testing is performed according to the intended use of the test in the intended patient population for which the test was developed and validated. Testing must be performed according to Clinical Laboratory Improvement Amendments (CLIA) and/or Food and Drug Administration (FDA) regulations in an accredited laboratory. For a given clinical indication (pre-OR post-biopsy), only one molecular biomarker may be performed UNLESS a second test, meeting all the criteria established herein, is reasonable and necessary as an adjunct to the first test, according to criteria established in this policy. If the test relies on an algorithm which may range in complexity from a threshold determination of a single numeric value to a complex mathematical or computational function, the algorithm must be validated in a cohort that is not a development cohort for the algorithm. The analytes measured have demonstrated clinical validity and clinical utility (i.e., improved detection or discrimination of cancer or high-grade cancer or reduction in the need for biopsy) in the peer-reviewed published literature, establishing a clear and significant biological/molecular basis for stratifying patients and subsequently selecting (either positively or negatively) their clinical management decision within a clearly defined population. The test is ordered by a physician specialist in the management of prostate cancer, such as a urologist or oncologist. An exception may be made in geographic locations where the specialist(s) cannot be reasonably reached by the beneficiary and the ordering provider is located closer to the beneficiary’s place of residence than the nearest specialist. We would generally expect that beneficiaries for whom the test is ordered under this exception to be living in rural locations, islands, or some other location where access to care is limited. NOTE: If the patient is considered higher risk (due to relevant family or personal cancer history, relevant high-risk genetic mutations, African ancestry, or other clinical parameters highly suspicious for cancer including a persistent and significant increase in PSA), a biopsy may still be warranted. These relative indications for biopsy should be taken into consideration as part of a shared decision-making process regarding whether to proceed with a biopsy. Analytical validity, clinical validity (of novel analytes), and clinical utility will be assessed as part of a thorough and comprehensive technical assessment (TA) by the Molecular Diagnostic Services Program (MolDX ® ).