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Considerations and FAQs

Insurance coverage considerations

Insurance coverage of NGS tests can vary. A few important factors to consider when ordering or coordinating patient access to NGS tests include1:

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Considerations, subhead

Frequently asked questions

When is the best time to test for HRR alterations?

Among tests recommended for prostate cancer patients, according to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), all patients with metastatic prostate cancer should be tested for HRR gene alterations.1

NCCN Guidelines® recommend1:

  • Testing for somatic HRR gene alterations upon metastatic prostate cancer diagnosis, and retesting may be considered upon progression to mCRPC
  • Testing for germline mutations in all PC patients with a positive family history of certain cancers or familial cancer risk mutation, high-risk localized or regional PC patients, and all metastatic PC patients
How should the multidisciplinary team coordinate with pathology?4-7
  • Oncologists and urologists need pathology’s perspective for accurate interpretation of results on each case, while pathologists need context from oncologists to provide actionable interpretation of results
  • For HRR alterations, discuss suitability of archived specimens and best approach for gathering new samples
  • Align on the order for the HRRm test. What genes will be tested? What additional analyses should be done?
  • Confirm how and where results will be sent. Results sent to pathology may be scanned and added to an unfamiliar location in the EHR, making the document hard to find and use. Coordinate with pathology for the interpretation, analysis, and actionability on the report
How should test results be interpreted?
Care team members should work closely with pathology and genetic counselors to extract the most meaningful and actionable information from testing results. Review the test result report for recommended treatment options for positive mutation results.7
What is CHIP, and what does it mean for testing?

NATIONAL COMPREHENSIVE CANCER NETWORK® (NCCN®) GUIDANCE ON ctDNA

NCCN Guidelines recommend a metastatic biopsy for histologic and molecular evaluation. This could include lymph node biopsy for patients with N1 disease. When unsafe or unfeasible, plasma circulating tumor DNA (ctDNA) assay is an option, preferably collected during biochemical (PSA) and/or radiographic progression in order to maximize diagnostic yield.1

Caution is needed when interpreting ctDNA-only evaluation due to potential interference from clonal hematopoiesis of indeterminate potential (CHIP), an age-related acquisition of somatic mutations that leads to clonal expansion in regenerating hematopoietic stem cell populations, which in turn can result in a false-positive biomarker signal.1,8

How can I streamline test result reporting?

By working closely with pathology, oncologists can ensure reports contain all universally understood nomenclature, allowing for integration into global patient- and cancer-specific databases along with data repositories to extract relationships between genetic variants and a patient’s health status.9

It's also important for oncology and pathology to work closely when developing a test report format, ensuring integration into the healthcare organization’s specific EHR.3

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CMS, Centers for Medicare and Medicaid Services; EHR, electronic health records; HRR, homologous recombination repair; HRRm, homologous recombination repair gene-mutated; mCRPC, metastatic castration-resistant prostate cancer; N1, metastasis in regional node(s); NGS, next-generation sequencing; PC, prostate cancer; PSA, prostate-specific antigen.

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed August 29, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Centers for Medicare and Medicaid Services. Next generation sequencing (NGS) for Medicare beneficiaries with advanced cancer. Updated January 27, 2020. Accessed July 3, 2024. https://www.cms.gov/medicare-coverage-database/view/ncacal-tracking-sheet.aspx?NCAId=296#:%7E:text=Specifically%2C%20the%20Centers%20for%20Medicare,and%20specific%20criteria%20are%20met
Szymaniak BM, Facchini LA, Giri VN, et al. Practical considerations and challenges for germline genetic testing in patients with prostate cancer: recommendations from the germline genetics working group of the PCCTC. JCO Oncol Pract 2020;16(12):811-19.
Gonzalez D, Mateo J, Stenzinger A, et al. Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer. J Pathol Clin Res 2021;7(4):311-25.
Schostak M, Bradbury A, Briganti A, et al. Practical guidance on establishing a molecular testing pathway for alterations in homologous recombination repair genes in clinical practice for patients with metastatic prostate cancer. Eur Urol Oncol 2024;7(3):344-54.
Shore ND, Morgans AK, El-Haddad G, et al. Addressing challenges and controversies in the management of prostate cancer with multidisciplinary teams. Targ Oncol 2022;17:709-25.
Hicks JK, Howard R, Reisman P, et al. Integrating somatic and germline next-generation sequencing into routing clinical oncology practice. JCO Precis Onc 2021;5:884-95.
He W, Xiao Y, Yan S, Zhu Y, Ren S. Cell-free DNA in the management of prostate cancer: current status and future prospective. Asian J Urol 2023;10(3):298-316.
Selvarajah S, Schrader KA, Kolinsky MP, et al. Recommendations for the implementation of genetic testing for metastatic prostate cancer patients in Canada. Can Urol Assoc J 2022;16(10):321-32.
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