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Considerations and FAQs

Insurance coverage considerations

Insurance coverage of NGS tests can vary. Important factors to consider when ordering or coordinating patient access to NGS tests include:

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Pre-test counseling (either in person or virtual) to address patient concerns over discrimination (eg, life insurance eligibility), testing methodology, and implications is recommended for germline testing. Informed decision-making and consent are critical and can be accomplished through video or in-person discussions and documented through well-developed forms. Post-test counseling is recommended if germline testing reveals any pathogenic/likely pathogenic variants prompting cascade testing in relatives or if a highly suspicious family history is not reflected in testing results.3–6

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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 mPC should be tested for HRR gene alterations.3

NCCN Guidelines® recommend:

  • Testing for somatic HRR gene alterations upon mPC diagnosis, and retesting may be considered upon progression to mCRPC3
  • Testing for germline mutations in all prostate cancer patients with a positive family history of certain cancers or familial cancer risk mutation and in all patients with very high-risk or high-risk localized, regional (node-positive), or mPC3,7
How should the multidisciplinary team coordinate with pathology?8–10

A pathologist's perspective can provide accurate interpretation of results, while context from the care team may provide insights or recommendations on subsequent testing.

For HRR alterations, discuss the suitability of archived specimens and the best approach for gathering new samples.

Align on the order for the HRRm test. Which genes will be tested? Which additional analyses (such as confirmatory germline testing) 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 of 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 positive mutation results and to assess treatment options.10
What is CHIP, and what does it mean for testing?

National Comprehensive Cancer Network® (NCCN®) guidance on ctDNA:

NCCN Guidelines strongly recommend a metastatic biopsy for histologic and molecular evaluation. This could include a lymph node biopsy for patients with N1 disease. When a biopsy is 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. When diagnostic yield is low, the risk of false negatives is higher, so ctDNA collection is not recommended when PSA is undetectable.3

Caution is needed when interpreting a 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.3,11

How can I streamline test result reporting?

By working closely with pathology, urologists and 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.12

It's also important for the multidisciplinary team to collaborate on how to optimally report and interpret results, ensuring integration into the healthcare organization's specific EHR.2

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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; mPC, metastatic prostate cancer; N1, metastasis in regional node(s); NGS, next-generation sequencing; PSA, prostate-specific antigen.

Centers for Medicare and Medicaid Services. Next generation sequencing (NGS) for Medicare beneficiaries with advanced cancer. Updated January 27, 2020. Accessed August 28, 2025. https://www.cms.gov/medicare-coverage-database/view/ncacal-tracking-sheet.aspx?NCAId=296
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.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V2.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed September 16, 2025. 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.
Armstrong AJ, Taylor A, Haffner MC, et al. Germline and somatic testing for homologous repair deficiency in patients with prostate cancer (part 1 of 2). Prostate Cancer Prostatic Dis. Published online October 1, 2024.
Cheng HH, Sokolova AO, Gulati R, et al. Internet-based germline genetic testing for men with metastatic prostate cancer. JCO Precis Oncol 2023;7:e2200104.
Russo J, McDougall C, Bowler N, et al. Pretest genetic education video versus genetic counseling for men considering prostate cancer germline testing: a patient-choice study to address urgent practice needs. JCO Precis Oncol 2021;5:PO.21.00238.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic and Prostate V1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 25, 2025. 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.
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, Srinivas S, Abramowitz M. Addressing challenges and controversies in the management of prostate cancer with multidisciplinary teams. Targ Oncol 2022;17(6):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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