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Genetics Can Inform Prostate Cancer Screening and Treatment

Genetics Can Inform Prostate Cancer Screening and Treatment
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Published on September 2, 2021

Don’t Discount Genetics in Prostate Cancer Care

Prostate cancer is the most commonly diagnosed cancer among men in the United States. Drugs have recently been approved to treat individuals with metastatic prostate cancer who have certain inherited mutations, and guidelines state that all people diagnosed with metastatic prostate cancer should consider genetic testing. Understanding genetics is also important for screening for prostate cancer and treating localized cancer if it is diagnosed, said Edward Schaeffer, MD, PhD, a urologist at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago in a virtual presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting held in June 2021.

“There are three inherited factors that impact a subject’s risk of being diagnosed with prostate cancer,” Dr. Schaeffer said. Family history is the oldest and most well-established risk factor. Most doctors say that someone has a family history of prostate cancer if the individual has three or more relatives who have had prostate cancer, or two or more relatives with early-onset prostate cancer. Prostate cancer is considered early-onset if it is diagnosed before age 55.

The association between family history and prostate cancer has been studied in largely white cohorts, Dr. Schaeffer said. However, work published in the April 2021 issue of Cancer Causes & Control demonstrated that family history is also a risk factor among Black men, he said. The researchers found that Black men with a family history of prostate cancer were likely to have particularly aggressive prostate cancers.

Rare inherited mutations, notably in the BRCA1 and BRCA2 genes, are also associated with an increased risk of prostate cancer, said Dr. Schaeffer. Mutations related to Lynch syndrome may also lead to elevated prostate cancer risk, and HOXB13 may be associated with early-onset prostate cancers. Individuals may be referred for genetic testing based on their family history, ancestry, or cancer history and characteristics.

Dr. Schaeffer also described several studies looking back at outcomes for prostate cancer patients with BRCA1 or BRCA2 mutations. Compared to patients without BRCA mutations, patients with these mutations are more likely to have higher-grade or higher-stage disease and to have cancer found in their lymph nodes and metastases at diagnosis, he said. Dr. Schaeffer cited a study of three-year, five-year, and 10-year metastasis-free survival rates, finding that they were 97%, 94%, and 84%, respectively, in patients without BRCA mutations, compared to 90%, 72%, and 50%, respectively, in patients with BRCA mutations. Dr. Schaeffer noted that these differences were likely mainly driven by BRCA2 mutations, rather than BRCA1 mutations.

In addition, researchers can look at differences in single DNA letters between people and make predictions about disease susceptibility based on analysis of multiple of these small differences, said Dr. Schaeffer. These differences are called single-nucleotide polymorphisms, or SNPs. Many studies have described SNPs associated with prostate cancer, and data from some studies suggest that combining assessment of SNPs with PSA-based prostate cancer screening can improve assessment of cancer risk, he said. However, evaluation of SNPs is not yet a routine part of screening and treatment, and Dr. Schaeffer noted that more studies are needed to validate their use.

Localized prostate cancer can be managed with a range of strategies, including active surveillance, surgery, or radiation, said Dr. Schaeffer. If patients know about any genetic mutations they have, it could help inform the decision of whether to follow a plan of active surveillance or a more aggressive management strategy, such as surgery or radiation, he said. Active surveillance consists of PSA blood tests and exams every six months and prostate biopsies every 12 to 24 months, Dr. Schaeffer explained.

“Although active surveillance is generally successful, with less than 0.1% progression to incurable disease, the safety of surveillance in men with rare pathologic variants has been questioned,” he noted.

For now, Dr. Schaeffer said, people considering prostate cancer screening or who have been diagnosed with prostate cancer can benefit from discussion of family history with their medical team. Patients and their doctors should also consider testing for rare genetic mutations that could shed light on risk, prognosis, and the best strategy for treatment.

–Heidi Splete

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