Germline Genetic Testing in Advanced Prostate Cancer; Practices and Barriers: Survey Results from the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium - Beyond the Abstract

Germline testing for prostate cancer (PCA) is revolutionizing treatment, management, and risk assessment. Pathogenic mutations in multiple DNA repair genes, and particularly BRCA2 and others, are informing targeted therapy options in the metastatic and advanced disease setting, active surveillance discussions in the early-stage setting, and PCA early detection discussions.1 Furthermore, germline testing may identify a spectrum of cancer risks important to address for men and their male and female blood relatives. Many thousands of men with PCA now meet criteria for germline testing due to expanded genetic testing guidelines.2 This rising demand for germline testing has created a relative shortage of genetic counseling impacting timely access to testing that can significantly impact treatment or management plans for men. As such, oncologists and urologists are now increasingly ordering germline testing in their practices, necessitating assessment of practice patterns and responsible implementation of germline testing for PCA.

Our publication “Germline Genetic Testing in Advanced Prostate Cancer; Practices and Barriers: Survey Results from the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium (PCCTC)”3 investigated practice patterns and barriers to germline testing among academic oncologists at PCCTC participating institutions. Key findings included that (62%) of oncologists at academic centers surveyed reported taking personal responsibility for some or all of the genetic education and testing of their patients with PCA. Furthermore, the majority of oncologists ordered comprehensive or large cancer panels, requiring that men understand considerations of larger panels such as testing of genes with a range of associated risk for PCA and some with limited guidance, higher rates of variants of uncertain significance with larger panels, potential to uncover multiple additional cancer risks beyond PCA, and the implications of test results for blood relatives.

A major practice need is a genetic education of oncologists and urologists in order to gain a working knowledge of germline testing, responsibilities of ordering providers, and familial impact.1 The collection of family history is a key aspect of germline testing and recommendations due to the hereditary nature of germline testing. Providers need to consider optimal ways to collect family history in their practices and how best to collaborate with genetic counselors to address comprehensive recommendations for men and their families. Laboratory selection for testing is critical. Choosing a lab with long-standing experience with germline testing, full gene sequencing, and assessment, a variant reclassification program, and panel options is important to identify pathogenic mutations and have long-term variant updates.

Some patients may need to see a genetics professional upfront due to complex family history, psychosocial needs, and insurance constraints. While several insurance plans cover genetic testing for PCA, many still do not cover testing for men with PCA or require a visit with a genetic counselor to cover testing. Men also need to understand the potential financial implications of testing, which is critical for men who are long-term PCA survivors or men who are otherwise healthy. The Genetic Information Nondiscrimination Act (GINA) of 2008 provides protections from genetic discrimination regarding health insurance and employment (except for small businesses with fewer than 15 employees). However, the GINA law does not cover long-term care, disability, or life insurance plans.

Finally, germline testing has implications regarding additional cancer risks for men and their families with potential management implications. For example, men with germline BRCA2 mutations may be at increased risk not only for PCA, but also pancreatic cancer, male breast cancer, and melanoma. Therefore, men with BRCA2 mutations would not only need PCA risk or treatment addressed, but also screening for male breast cancer with clinical breast exams and pancreatic cancer screening if there is also a family history of pancreatic cancer. Female relatives who inherit BRCA2 mutations are at increased risk for cancers of the breast, ovary, pancreas, and melanoma with significant management and risk reduction decisions to consider.4 Thus, oncology and urology practices who undertake ordering germline testing need to have mechanisms in place either within their practices or in collaboration with genetic counselors to address these and many other genetically-related issues.

New initiatives are emerging to enhance the field of germline testing for PCA. Technology-based tools may be helpful in facilitating family history collection, genetic education, and identification of men with PCA for germline testing. Dr. Giri is leading a team of investigators to develop a mobile-friendly tool for providers regarding germline PCA testing. This tool will undergo user testing as part of the Technology-enhanced AcceleRation of Germline Evaluation for Therapy – The TARGET study, a nationally-funded study from the Prostate Cancer Foundation (2019 Prostate Cancer Foundation VAlor Challenge Award - Principal Investigator: Giri and Co-Principal Investigator: Loeb). Similarly, Dr. Paller and Dr. Cheng are leading the PROMISE registry: A Prostate Cancer Registry of Outcomes and Germline Mutations for Improved Survival and Treatment Effectiveness with the help of the PCCTC which will focus on identification, recruitment, and treatment response of germline carriers and selected variants of uncertain significance in genes of interest.5

The registry will help provide education about genes and match patients with the proper treatment or trial based on their mutation. Dr. Giri is leading the upcoming Prostate Cancer Genetic Risk, Experience, and Support Study: PROGRESS Registry. This national registry will collect information from men who have had germline testing for PCA and assess their experience with testing from various clinical settings to rapidly inform responsible PCA germline testing. Furthermore, the 2019 Philadelphia Prostate Cancer Consensus Conference addressed implementation of germline testing for PCA, focused on topics such as optimal testing strategies, testing indications, and alternate genetic evaluation models to meet the needs of men with PCA and their families regarding germline testing.6 Results from the conference will be forthcoming in publication.

In summary, these are exciting times regarding the expanding role of germline testing for men with PCA to inform treatments and management. This precision medicine era mandates greater collaboration between healthcare providers and genetic specialists for optimal genetic evaluation of men and their families.

Written by: Veda N. Giri, MD, Associate Professor, Director of Jefferson Clinical Cancer Genetics Service, Jefferson University Physician, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; Heather H. Cheng, MD, PhD, Director of the Prostate Cancer Genetics Clinic, Seattle Cancer Care Alliance, Associate Professor, Division of Medical Oncology, University of Washington School of Medicine, Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Channing J. Paller, MD, Medical Oncologist, Sibley Memorial Hospital, Washington D.C., USA, Associate Professor of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland

References:

  1. Giri, Veda N., Colette Hyatt, and Leonard G. Gomella. "Germline testing for men with prostate cancer: navigating an expanding new world of genetic evaluation for precision therapy and precision management." (2019).
  2. National Comprehensive Cancer Network. "NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer V. 4." 
  3. Paller, Channing J., Emmanuel S. Antonarakis, Tomasz M. Beer, Hala T. Borno, Maria I. Carlo, Daniel J. George, Julie N. Graff et al. "Germline genetic testing in advanced prostate cancer; practices and barriers: survey results from the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium." Clinical genitourinary cancer 17, no. 4 (2019): 275-282.
  4. National Comprehensive Cancer Network. "NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Genetic/familial high-risk assessment: Breast and ovarian [v. 1.2018]."
  5. Cheng, Heather H., Alexandra O. Sokolova, Edward M. Schaeffer, Eric J. Small, and Celestia S. Higano. "Germline and somatic mutations in prostate cancer for the clinician." Journal of the National Comprehensive Cancer Network 17, no. 5 (2019): 515-521.
  6. Gomella, Leonard G., Karen E. Knudsen, and Veda N. Giri. "Introduction to the 2019 Philadelphia Prostate Cancer Consensus Program:'Implementation of Genetic Testing for Inherited Prostate Cancer'." The Canadian journal of urology 26, no. 5S2 (2019): 1-4.
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