Transparency Submission

FDA Clearance: N/A

Rationale for Requested Change: With the recent change to the NCCN Prostate Cancer guidelines1, in which pre-test guidelines for germline testing were removed and clinicians are now directed to the Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic (HBOP)2 and Genetic/Familial High-Risk Assessment: Colorectal (Lynch syndrome) guidelines3, it is imperative that Prostate Cancer is added to the title of the HBOP guidelines. This will help prostate cancer clinicians recognize that the content in these guidelines inform eligibility for germline testing for patients with prostate cancer. With as many as 1 in 5 patients harboring pathogenic germline variants,4–9 prostate cancer is one of the most common hereditary cancers, along with breast, ovarian, pancreatic and colorectal cancer. All of the aforementioned cancers are called out in the titles of the respective Genetic/Familial High-Risk Assessment Guidelines; again, prostate cancer should not be the exception. It is particularly important to increase visibility of the genetic component of prostate cancer PCa has one of the lowest rates of germline genetic testing (GGT) uptake, with just 1% of affected individuals undergoing GGT in one study.10 Even in patients with metastatic and/or castration-resistant disease, where GGT is universally recommended, rates of uptake are documented to be as low as 4-13%.10,11 GGT utilization is even worse among non-White, rural, and poorer PCa patient populations.10,12 A systematic review by Briggs et al found that only 7.2% of men undergoing GGT for PCa were Black, significantly less than the 13.4% of the U.S. population that is Black.12 Additionally, GGT is still a relatively new clinical area for genitourinary healthcare providers, and increased genetics education for clinicians treating patients with prostate cancer is crucial to address this gap.13 However, highlighting prostate cancer in the title of the NCCN guidelines reiterates its importance in hereditary cancer risk assessment and testing. Furthermore, there is a general lack of understanding among patients and providers that some of the same genes that predispose to breast and ovarian cancer can also increase prostate cancer risk, and vice versa.14–20 More explicitly stating that these cancers can be related could help clinicians to take more comprehensive family histories and maximize the benefits of cascade testing. Awareness of risks are critical as some of these cancers may be prevented through risk-reducing surgery or medication (e.g., mastectomy, hysterectomy, salpingo-oophorectomy, and/or chemoprevention).2,3 We greatly appreciate the invaluable clinical resource the NCCN guidelines are for the management of patients with prostate cancer and thank you for considering our proposal in the context of the evidence reviewed. Sincerely, Neal Shore, MD, FACS Medical Director, Carolina Urologic Research Center Chief Medical Officer, Surgery/Urology, GenesisCare Atlantic Urology Clinics W. Michael Korn, MD Chief Medical Officer, Invitae Corporation Edward D. Esplin, MD, PhD Clinical Geneticist, Invitae Corporation Sarah Young, CGC Oncology Clinical Program Manager, Invitae Corporation Emmanuel S. Antonarakis, MD Clark Endowed Professor of Medicine Director of GU Oncology, Associate Director of Translation Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center Andrew J. Armstrong, MD ScM FACP Professor of Medicine, Surgery, Pharmacology and Cancer Biology Director of Research, the Duke Cancer Institute Center for Prostate and Urologic Cancers Divisions of Medical Oncology and Urology, Duke University Pedro C. Barata, MD, MSc Co-Leader Genitourinary (GU) Disease Team Director of GU Medical Oncology Research Program University Hospitals Seidman Cancer Center Associate Professor of Medicine, Case Western Reserve University Case Comprehensive Cancer Center Tomasz M. Beer, MD, FACP Adjunct Professor of Medicine, Oregon Health & Science University Knight Cancer Institute Chief Medical Officer for Multi-cancer Early Detection, Exact Sciences Corporation Elisabeth I. Heath, MD FACP Associate Center Director, Translational Sciences Chair, Genitourinary Oncology Multidisciplinary Team Professor of Oncology and Medicine Hartmann Endowed Chair for Prostate Cancer Research Director, Prostate Cancer Research Karmanos Cancer Institute Brian Helfand, MD Chief, Division of Urology, NorthShore University HealthSystem Clinical Professor, University of Chicago Maha Hussain, MD, FACP, FASCO Genevieve Teuton Professor of Medicine Division of Hem/Onc Deputy Director, Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Rana Mckay, MD Associate Professor of Medicine, University of California San Diego Alicia K. Morgans, MD, MPH Associate Professor of Medicine, Harvard Medical School Medical Director, Survivorship Program Dana-Farber Cancer Institute Ashley E Ross, MD, PhD Associate Professor, Urology Northwestern Feinberg School of Medicine Matthew R. Smith, MD, PhD Director, Genitourinary Malignancies Program Massachusetts General Hospital Cancer Center David Wise, MD, PhD Director – Genitourinary Medical Oncology Program NYU Langone’s Laura and Isaac Perlmutter Cancer Center