In This Article
- A new clinic from the Massachusetts General Hospital Department of Urology and Mass General Cancer Center offers genetic testing and enhanced screening for patients at high risk of developing prostate cancer
- A new study open for enrollment is evaluating multiparametric prostate MRI as a screening tool for high-risk men and exploring novel biomarkers for early detection of prostate cancer
- Research study on active surveillance for prostate cancer suggests an increased risk of progression to aggressive disease among men with a strong family history of not only prostate cancer but also a cluster of related cancers: breast, ovarian and pancreatic
While it is well-recognized that prostate cancer has a significant heritable component, the role of genetics in disease prediction, diagnosis and treatment is gaining increased attention. In his dual role of urologic oncologist and geneticist, Keyan Salari, MD, PhD, urologic surgeon at the Massachusetts General Hospital Department of Urology and urologic oncologist with the Mass General Cancer Center, is exploring the genetic drivers of prostate cancer through a new clinic and extensive research.
"There is an underappreciated role of genetics in the predisposition to prostate cancer," Dr. Salari says. "We've always known that prostate cancer can run in families, but only recently are we understanding how to translate the genetic underpinnings of the disease into clinical practice."
He integrates his research in a new clinic offering genetic testing and enhanced screening for patients with a high risk of aggressive prostate cancer.
New Prostate Cancer Clinic Offers Genetic Testing
In October 2020, Dr. Salari launched a new clinic within Mass General's Department of Urology that offers expanded genetic testing for men not diagnosed with prostate cancer but who carry a high genetic risk for developing the disease.
"We are testing men who are at high risk of developing prostate cancer based on either a strong family history or a known inherited genetic mutation in the family that predisposes them to prostate cancer," he says.
Candidates for genetic testing in the new Prostate Cancer High-Risk Clinic include men with a family history of not only prostate cancer but also cancers like breast, ovarian and/or pancreatic cancer that are suggestive of a hereditary syndrome. Research indicates that men with a cluster of these familial cancers may be at higher risk of aggressive prostate cancer.
Dr. Salari created the new clinic in response to the demand for genetic testing. Indications for genetic testing for prostate cancer are expanding rapidly, and demand is outpacing the supply of genetic counselors.
"This new clinic changes the model of how we do genetic testing," he says.
Working in close collaboration with the Center for Cancer Risk Assessment in the Mass General Cancer Center, patients referred to the clinic receive upfront physician-directed testing and counseling. Once test results return, all patients receive post-test counseling with a genetic counselor in the Prostate Cancer Genetics Clinic, where Dr. Salari also serves as co-director. If testing identifies a deleterious genetic mutation, patients are referred to a team of high-risk cancer specialists for expanded screening based on the specific genetic findings.
Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)
Running in parallel with the new clinic is a novel study investigating the early detection of prostate cancer among high-risk men, entitled "Prostate Cancer Genetic Risk Evaluation and Screening Study" (PROGRESS). Dr. Salari and partners will enroll up to 500 men aged 35 to 75 who do not have prostate cancer but carry a high risk due to family history (cohort 1) or a known genetic mutation (cohort 2). The study has two aims:
- Evaluate the efficacy of multiparametric magnetic resonance imaging (mpMRI) of the prostate as a form of enhanced screening for prostate cancer, in addition to the standard prostate-specific antigen (PSA) blood test and prostate examination
- Identify novel genetic risk mutations and discover novel molecular and genetic biomarkers for early detection
Study participants will undergo a baseline clinical evaluation and annual evaluations, including a comprehensive history and physical examination, digital rectal exam of the prostate and serum PSA testing. At enrollment and every three years, participants will have a mpMRI of the prostate.
Impact of Genetics on Outcomes of Active Surveillance for Prostate Cancer
Mass General is one of the nation's leaders in offering active surveillance (AS) for slow-growing, low-risk prostate cancer. Active surveillance is the preferred management strategy to monitor low-risk disease while avoiding the side effects and risks of unnecessary surgery and radiation.
Dr. Salari reports that approximately one in three men on AS for prostate cancer progress to requiring treatment within five years and half progress within 10 years. "There is an urgent unmet need to reliably distinguish indolent from aggressive prostate cancer and improve how we select patients for AS," he says. With Mass General's institutional expertise and Dr. Salari's background in urologic oncology and genetics, he investigated applications of genetics to the outcomes of AS for prostate cancer.
In December 2020, Dr. Salari and colleagues presented a study, "The Impact of a Positive Family History on Clinical and Pathologic Outcomes of Active Surveillance for Prostate Cancer" at the Society of Urologic Oncology Annual Meeting.
"We looked at not just a family history of prostate cancer, but also a family history of prostate, breast, ovarian and pancreatic cancer, specifically for this study," he says. "One key takeaway was that having a strong family history of prostate cancer alone did not increase the risk of progression on active surveillance, but having a strong family history of prostate, breast, ovarian, and/or pancreatic cancer—suggesting an inherited cancer syndrome—did increase the risk of disease progression on active surveillance."
According to Dr. Salari, this study suggests that men with such a family history may still be offered AS safely but should receive counseling about the higher risk of progression.
Increasing the Accessibility of Genetics Testing for Prostate Cancer
One of Dr. Salari's goals is to make genetic testing more accessible. "Genetic testing is a complex undertaking, so we want to make sure we have appropriate counseling, testing and interpretation of results because these have significant implications for patients and their families. We hope to do this in a comprehensive and systematic way with our multi-disciplinary team."
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