Hereditary Prostate Cancer—What Urologists Should Know

Lawrence I. Karsh, MD
Published: Friday, Feb 15, 2019
Lawrence I. Karsh, MD

Lawrence I. Karsh, MD

Prostate cancer is the most prevalent solid tumor in men over 50 years of age and the second-leading cause of cancer-specific mortality in the United States today. It was estimated that in 2018 alone, 165,000 men would be given a diagnosis of prostate cancer and more than 29,000 men would die from the disease.1 Most cases are localized at the time of diagnosis, but de novo metastatic disease is on the rise and may represent 4% of initial presentations. The median ages at diagnosis and death are 66 and 80 years, respectively. The statistics are worse for African American men, who are nearly twice as likely as Caucasian men to develop prostate cancer and more than twice as likely to die of the disease.2 In addition, African American men with prostate cancer are more likely than Caucasian men (7.3% vs 2.2%) to have mutations in the DNA repair genes BRCA1 and BRCA2 and thus experience more aggressive prostate cancer with a shorter time to metastasis.3 Estimates vary, but 20% to 30% of all men treated for localized disease develop biochemical recurrence and eventually progress to terminal metastatic castration-resistant prostate cancer (mCRPC).4

Historically, urologists have been the primary caretakers for men with localized prostate cancer. The first decade of the 21st century heralded a renaissance of drug development for the management of patients with mCRPC. Seven new therapies gained FDA approval for both metastatic and nonmetastatic CRPC. Many of these agents are oral and have a very manageable adverse event profile. As a result, urologists have become more active in the delivery of oncologic care across the spectrum of prostate cancer, even for patients with advanced prostate cancer.

In March 2007, the US Department of Health & Human Services launched the Personalized Health Care Initiative with the goal of integrating gene-based technologies into healthcare delivery so that therapies would be better tailored to individual patients.5 A year later, with the goal of barring the use of genetic information in health insurance or employment, Congress enacted the Genetic Information Nondiscrimination Act (GINA). Although far from perfect, it prevents employers from using genetic information as the basis for denial of health insurance and decisions about hiring, firing, and promotions.

The drive toward precision medicine has resulted in a deeper understanding of the molecular biology of cancer development. There are still gaps in the understanding of the respective roles of genetics and gene mutations, diet, and the environment. These factors, particularly the genetic component, are key to malignant cell development and, ultimately, cancer. As a result, there is a growing need to incorporate genetic counseling and testing into comprehensive cancer care.

Along these lines, urologists are becoming more and more aware that lethal prostate cancer has a distinct hereditary component. Just as hereditary testing has been incorporated into comprehensive care models for many specialties, this evolving platform must now be incorporated into advanced prostate cancer care. The tools for doing this are becoming increasingly available. The FDA recently approved a next-generation sequencing (NGS) testing panel for several hundred genes in solid tumors, thus advancing the current era of personalized molecular oncology. This test may justify the use of specific therapies across tumor types, regardless of initial labeling.

Although the term genetics has traditionally comprised individual genes and their inheritance patterns (some diseases, such as sickle cell anemia and cystic fibrosis, result from alterations in an isolated gene), the modern definition includes multiple gene inheritance patterns. Thus, modern genetic testing relies on genomics, encompassing an organism’s entire genetic makeup (genome) and an extensive number of genes interacting with one another and the environment.

Germline mutations are almost always inherited. They are present in every cell of the body but only half of all eggs and sperm. A child of a germline mutation carrier has a 50% chance of inheriting that gene. Multigene panels evaluate blood or saliva cells for the presence of these germline mutations. Somatic mutations develop when a cell becomes malignant. These changes can be found only in the tumor. When a germline mutation is present in a tumor suppressor gene, such as BRCA, it may accelerate the accumulation of somatic mutations, thus increasing the chance that cancer will develop.

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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis SyndromeJun 30, 20191.0
Community Practice Connections™: 2nd Annual International Congress on Oncology Pathology™Aug 31, 20191.5
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