Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38649)

CMS National Coverage PolicyTitle XVIII of the Social Security Act (SSA), 1862(a)(1)(A), states that no Medicare payment shall be made for items or services that are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.42 Code of Federal Regulations (CFR) 410.32 Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, 80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests, 80.1.1 Certification ChangesCoverage Indications, Limitations, and/or Medical NecessityThis contractor will cover molecular diagnostic tests for use in a beneficiary with bladder cancer when all of the following conditions are met:The beneficiary is being actively managed for bladder cancer.The beneficiary is within the population and has the indication for which the test was developed and is covered. The lab providing the test is responsible for clearly indicating to treating clinicians the population and indication for test use.At least 1 of the 2 criteria are met:The patient is a candidate for multiple potential treatments, which could be considered to have varied or increasing levels of intensity based on a consensus guideline, and the physician and patient must decide among these treatments.ORThe patient is a candidate for multiple therapies, and the test has shown that it predicts response to a specific therapy among accepted therapy options based on nationally recognized consensus guidelines.The test demonstrates analytical validity including both analytical and clinical validations. 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 test has demonstrated clinical validity and utility, establishing a clear and significant biological/molecular basis for stratifying patients and subsequently selecting (either positively or negatively) a clinical management decision (in 4. above) in a clearly defined population.The test successfully completes a Molecular Diagnostic Program (MolDX) technical assessment that ensures the test is reasonable and necessary as described in 4 and 5 above.General InformationAssociated InformationN/ASources of InformationN/ABibliographySiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021.CA Cancer J Clin.2021;71(1):7-33.Flaig TW, Spiess PE, Agarwal N, et al. Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology.J Natl Compr Canc Netw.2020;18(3): 329-354.Svatek RS, Shariat SF, Novara G, et al. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort.BJU Int.2011;107(6):898-904.U.S. Food and Drug Administration (FDA).Balversa prescribing information. Accessed April 20, 2022.Helpap B. Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract.Cancer.2002;95(7):1415-1420.Ali SZ, Reuter VE, Zakowski MF. Small cell neuroendocrine carcinoma of the urinary bladder: a clinicopathologic study with emphasis on cytologic features.Cancer.1997;79(2):356-361.National Cancer Institute. Cancer Stat Facts: Bladder Cancer.https://seer.cancer.gov/statfacts/html/urinb.htmlAccessed April 20, 2022.Seiler R, Ashab HAD, Erho N, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy.Eur Urol.2017;72(4):544-554.Lotan Y, Boorjian SA, Zhang J, et al. Molecular subtyping of clinically localized urothelial carcinoma reveals lower rates of pathological upstaging at radical cystectomy among luminal tumors.Eur Urol.2019;76(2):200-206.Batista da Costa J, Gibb EA, Bivalacqua TJ, et al. Molecular characterization of neuroendocrine-like bladder cancer.Clin Cancer Res.2019;25(13):3908-3920.Fryback DG, Thornbury JR. The efficacy of diagnostic imaging.Med Decis Making.1991;11(2):88-94.Centers for Disease Control and Prevention. ACCE Model List of 44 Targeted Questions Aimed at a Comprehensive Review of Genetic Testing.https://www.cdc.gov/genomics/gtesting/acce/acce_proj.htm. Accessed April 20, 2022.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Bladder Cancer, Version 6.2021.https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed April 20, 2022.Ross JS, Wang K, Khaira D, et al. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.Cancer. 2016;122(5):702-711.Mori K, Abufaraj M, Mostafaei H, et al. A systemic review and meta-analysis of variant histology in urothelial carcinoma of the bladder treated with radical cystectomy.J Urol.2020;204(6):1129-1140.US Food and Drug Administration (FDA). Prescribing Information. BALVERSA (erdafitinib). 2020.https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212018s001lbl.pdf. Accessed April 20, 2022.Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma.N Engl J Med.2019;381(4):338-348.