Genetic Testing in Prostate Cancer: Challenges and Solutions
By: Stacy Loeb, MD, MSc, PhD (hc); Veda N. Giri, MD | Posted on: 01 Sep 2022
Germline genetic testing is playing an increasingly important role in prostate cancer care across the spectrum of disease. Carriers of pathogenic variants in genes such as BRCA2 are recommended to undergo earlier screening for prostate cancer.1 Many of the same germline variants also affect treatment recommendations and clinical trial eligibility, particularly in advanced disease. In addition to the importance of germline results for prostate cancer care, they also have significant implications for hereditary cancer screening in patients and their relatives.
However, germline testing is currently underutilized among men with prostate cancer.2 We recently published a qualitative study reporting on many barriers to germline testing at the patient, physician, organizational, and societal levels.3 To address some of the major challenges, we are currently in the midst of several studies which will be highlighted in this article.
Technology-Enhanced AcceleRation of Germline Evaluation for Therapy (TARGET) Study
One of the major challenges with scaling up genetic testing for prostate cancer is a relative shortage of genetic counselors needed to evaluate the rapidly rising volume of patients in need of genetic evaluation, creating a bottleneck in the process. In collaboration with the Prostate Cancer Foundation and funded by a 2019 Prostate Cancer Foundation Challenge Award, we developed a patient-driven interactive Web tool to deliver pre-test genetic education. The Web tool contains 9 modules, spanning topics including basics of cancer genetics and inheritance, genetic basis of prostate cancer, risk factors for prostate cancer, options for germline testing, types of test results, genes to be tested, benefits/risks/limitations of testing, management based on test results, genetic discrimination laws, and implications for relatives. Participants can complete the modules on their own, and each one is followed by a series of knowledge questions to verify understanding of the information.
Once the Web tool was developed and optimized, we initiated the TARGET randomized trial to assess whether use of the Web tool for pre-test education is noninferior to standard pre-test counseling with a genetic counselor. Full details of the study protocol were recently published.4 The TARGET study has just completed enrollment, and analysis is underway. If successful, this tool could provide a scalable method to facilitate the provision of pre-test genetic education. This could reduce the burden for genetic counselors, and save their valuable time to provide pre-test counseling to patients with clinical complexity or psychosocial needs, and to counsel patients about test results and clinical implications.
The TARGET study also included development and testing of Helix, a mobile-friendly website for health care providers with information about genetic counseling and genetic testing, as well as an interactive tool to help identify which patients to consider for genetic testing. Helix provides educational modules covering core topics including basics of cancer genetics and inheritance, genetic basis of prostate cancer, risk factors for prostate cancer, options for germline testing, types of test results, genes to be tested, benefits/risks/limitations of testing, management based on test results, genetic discrimination laws, and implications for relatives in text and audio formats. Helix underwent successful user testing by a spectrum of providers,5 and is now publicly available at helix.guide.
Other major challenges with the implementation of germline testing are the variable education and exposure of health care providers to genetic testing, as well as the ever-evolving landscape of precision oncology care. To address these education and practice gaps, we developed a Virtual Genetics Board with support from a 2019 Department of Defense Idea Development Award. The Virtual Genetics Board includes case-based discussions with a multidisciplinary panel about patients with prostate cancer and management of genetic results. These meetings were conducted monthly from July 2021 to March 2022, and were open to U.S. health care providers, scientists, and other stakeholders for live participation.
In addition, all of the episodes are archived online (www.prostategenetics.com/engagement) to provide a lasting repository of content on the optimal integration of genetics into prostate cancer care. We invite any AUANews readers to participate in the study by viewing the recordings and answering some questions to ensure value and use of this modality of genetics knowledge dissemination. Key topics include the indications for germline testing, pre-test education and informed consent, interpretation of results, precision management, case complexities encountered in practice, and cascade testing. To register, go to www.prostategenetics.com/engagement.
A rapidly evolving area of prostate cancer treatment includes targeted therapy for men with metastatic prostate cancer based on genomic test results on tumors or in the germline. Two PARP inhibitors (olaparib and rucaparib) are Food and Drug Administration-approved for the treatment of men with metastatic, castration-resistant prostate cancer with DNA repair gene mutations after progression on initial lines of therapy. There are many open questions regarding which patients may be optimal candidates for PARP inhibitors, which genes may predict optimal response, and which modalities of testing predict clinical responses. The PRECISION Registry, funded by a 2020 Prostate Cancer Foundation Challenge Award, is an international effort to build a large registry of men with metastatic, castration-resistant prostate cancer across clinical cohorts, academic centers, and clinical trials to gain deeper insights into PARP inhibitor responses. To collaborate, please contact www.precision-registry.com.
- Giri VN, Knudsen KE, Kelly WK, et al. Implementation of germline testing for prostate cancer: Philadelphia Prostate Cancer Consensus Conference 2019. J Clin Oncol. 2020;38(24):2798-2811.
- Loeb S, Byrne N, Walter D, et al. Knowledge and practice regarding prostate cancer germline testing among urologists: gaps to address for optimal implementation. Cancer Treat Res Commun. 2020;25:100212.
- Loeb S, Li R, Sanchez Nolasco T, et al. Barriers and facilitators of germline genetic evaluation for prostate cancer. Prostate. 2021;81(11):754-764.
- Loeb S, Cheng HH, Leader A, et al. Technology-enhanced AcceleRation of Germline Evaluation for Therapy (TARGET): a randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing. Contemp Clin Trials. 2022;119:106821.
- Giri VN, Walker A, Gross L, et al. Helix: a digital tool to address provider needs for prostate cancer genetic testing in clinical practice. Clin Genitourin Cancer. 2022;20(2):e104-e113.