An international expert panel has developed a comprehensive, multidisciplinary consensus statement for the genetic evaluation of inherited prostate cancer (PCa) in the multigene testing era, according to a new report.
The goal of the consensus statement, which was published online ahead of print in the Journal of Clinical Oncology, is to provide a focused and balanced clinical approach to genetic testing, genetic counseling, and genetically-informed screening and management for men with PCa relevant to urologists, oncologists, primary care providers, clinical cancer genetics specialists, and genetic counselors.
“Urologists are often on the front lines of diagnosis and treatment of prostate cancer,” said lead author Veda N. Giri, MD, Director of Cancer Risk Assessment and Clinical Cancer Genetics in the Department of Medical Oncology at Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, told Renal & Urology News. “These consensus recommendations point to the need to obtain family history information regarding cancers in males and female relatives on the maternal and paternal sides of the family when evaluating and treating men with prostate cancer.”
With this information, urologists could assess whether men should be referred for genetic counseling and testing. These cancers include prostate, breast, ovarian, colorectal, uterine, and pancreatic cancers and melanoma.
A man’s relatives may benefit
A genetic test could reveal mutations that may impact a son, daughter, sister, brother or other relatives and reveal higher risks of cancer across a family. “As data emerge, genetic testing for inherited mutations may increasingly be used in the conversation that urologists have with patients regarding management of localized prostate cancer, and therefore there is a need for increased collaboration between urologists and cancer genetic specialists,” Dr Giri said.
Up to 15% of prostate malignancies may be inherited, and at least some of the genes that confer inherited risk are known and testable.
Guidelines for genetic counseling and genetic testing for PCa are limited and focus only on testing of BRCA1 and BRCA 2, the consensus statement authors pointed out. They noted that National Comprehensive Cancer Network (NCCN) Genetic Familial High-Risk Assessment: Breast and Ovarian (Version 2.2017) guidelines, published in the Journal of the National Comprehensive Cancer Network (2017;15:9-20), address testing BRCA1 and BRCA2 for men with a personal history of PCa limited to Gleason 7 or higher with specific family history features, or metastatic prostate cancer. The NCCN guidelines, however, do not specifically address other genes now available for testing via multigene panels, some of which are implicated in PCa predisposition.
Personalized therapy possible
Senior author Leonard Gomella, MD, Chair of Urology and Clinical Director of the Sidney Kimmel Cancer Center Network at Thomas Jefferson University, said the consensus panel was convened to fill a significant gap in current guidelines. “Genetic testing for inherited PCa may help optimize and personalize treatment, but it also reveals information that can impact entire families and older and younger generations,” Dr Gomella said. Commercially available genetic tests for inherited PCa risk can cover from 10 to 14 genes that can inform clinical decision making.
The new guidelines are a product of the Philadelphia Prostate Cancer Consensus Conference 2017 hosted by Sidney Kimmel Cancer Center. Participants included specialists in urology, clinical cancer genetics and genetic counseling, medical and radiation oncology, primary care, and researchers. Gynecologic oncology and breast cancer specialists, patient advocates, and bioethicists also participated.
“Without this consensus review, it is difficult to capture who should be referred for genetic counseling and testing,” Dr Gomella said. It is important to determine who may need to be monitored more closely and which men may need to start PCa screenings earlier than recommended in general screening guidelines.
PCa patients with inherited mutations in the BRCA2, BRCA1, and ATM genes may respond to poly ADP ribose polymerase (PARP) inhibitors, especially if their disease has metastasized and is resistant to initial treatments, according to the guidelines. The consensus panel agreed with other national organizations that men with metastatic PCa should be considered for genetic counseling and genetic testing to determine if their PCa was inherited.
The consensus statement also expanded considerations of PCa screening and management of early-stage disease based on genetic test results, which was a gap in current guidelines. The expert panel arrived at a moderate consensus for BRCA2 testing in early-stage management discussion, but reached a stronger consensus for this testing in the high-risk/advanced and metastatic setting. Panel members were in moderate agreement with respect to testing all men with metastatic castration-resistant disease, regardless of family history.
Areas in critical need of further research identified by the consensus panel include genetic testing in African-American men, greater understanding of the genetic basis for aggressive prostate cancer, genetically-informed management and outcomes in early-stage disease, and the economic impact of genetic testing for PCa.
Dr Gomella said this new set of recommendations may help lower morbidity and mortality among PCa patients. “By identifying family members of the potential for inherited prostate cancer risk, screening can be started earlier in life than has been traditionally recommended. Further, these inherited prostate cancer genes appear to identify men who are the best candidates for new targeted drug therapies if the cancer becomes advanced,” Dr Gomella said.
Yair Lotan, MD, Professor and Chief of Urologic Oncology at the University of Texas Southwestern Medical Center in Dallas, said the new recommendations may significantly benefit urologists because this is an area where the literature is evolving or contradictory. “I think it adds some clarity on which groups need testing and what tests to consider,” Dr Lotan said. “The main point of the guidelines is to identify patients at risk and refer them to genetic counselors for discussion of testing. It also informs on what tests should be considered at this time. The actual tests will likely evolve over time so the current list will likely change in the future.”
Zachary Hamilton, MD, Assistant Professor of Urology at Saint Louis University in Missouri, said the consensus statement fills a previous gap in urologic oncology guidelines. PCa screening guidelines have been evolving and now place more emphasis on selective and informed screening, especially for men at highest risk for aggressive disease.
“While routine genetic testing may not be ready for daily clinical practice, this consensus statement provides expert opinion on how to best incorporate the current knowledge base,” Dr Hamilton said. “With more time and additional research, genetic testing will be adapted into treatment guidelines by major organizations. Until then, this consensus statement provides a framework for urologists who treat prostate cancer.”
Giri VN, Knudsen KE, Kelly WK, et al. Role of genetic testing for inherited prostate cancer risk: Philadelphia Cancer Consensus Conference 2017. J Clin Oncol. 2017; published online ahead of print.
Veda N. Giri, MD, is Director of Cancer Risk Assessment and Clinical Cancer Genetics in the Department of Medical Oncology at Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia.
Leonard Gomella, MD, is Chair of Urology and Clinical Director of the Sidney Kimmel Cancer Center Network at Thomas Jefferson University in Philadelphia.