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Nearly 165,000 men in the US developed prostate cancer in 2018, and about 29,500 of these men will most likely die of it. Black men are at a higher risk, as are men with a family history of prostate cancer, particularly if a father, brother, or multiple male family members had the disease. Until recently, Prostate exams and PSA tests have been the only screening tools for prostate cancer in men.
“Genetic testing was not done for men because we lacked data on who to test and what to test for,” said Elias Obeid, MD, MPH, a clinical cancer geneticist at Fox Chase Cancer Center. “We now know that there is a higher incidence of prostate cancer in men with certain mutations of the DNA repair genes, including BRCA1, BRCA2, ATM, PALB2, and FANCA.”
In the past few years, specific germline mutations have been identified in a high frequency in men with metastatic prostate cancer. In one study, a significant proportion of patients with such mutations and castration-resistant metastatic prostate cancer responded to PARP inhibitor therapy. This suggests that genetic tests for defects in DNA-damage repair genes can identify individuals and families with a predisposition to prostate cancer, as well as stratify patients for targeted therapies using a PARP inhibitor or clinical trial eligibility.
The findings from those and other studies were compelling enough for NCCN guidelines to recommend genetic testing for all men with metastatic prostate cancer.
“Most of the genes identified are already included in the genetic testing panels used for women with breast cancer,” Obeid said. “The question of when in the process of the disease to test has not yet been addressed. Some physicians test early on, others test later when they are selecting other treatment options.”
New NCCN guidelines also address the link between prostate cancer and Lynch Syndrome. Physicians should consider tumor testing for MMR deficiency and MSI-H, and if found, patients can be considered for immunotherapy and referred to genetic counseling to be assessed for Lynch Syndrome.
Some patients with non-metastatic prostate cancer and certain family cancers should be referred for genetic counseling and screened for colon and other related cancers. The NCCN guidelines help physicians in selecting those patients.
NCCN guidelines also recommend cancer risk assessment and genetic counseling in tandem with genetic testing.
“Genetic counselors help patients and families understand the clinical implications of the results,” Obeid said. “Relaying the results without a detailed explanation is insufficient. For patients with metastatic cancer, appropriate interpretation of the results may change their care and also affect their families.”
The guidelines also recommend genetic counseling for non-metastatic prostate cancer depending on Gleason score and family history.
“Genetic counseling can inform a patient of which screenings they may need for other cancers, such as skin, pancreatic, and male breast cancer.” Obeid said.
Three Things to Know About Genetic Testing and Prostate Cancer:
1. Results affect treatment decisions for patients with metastatic prostate cancer.
2. Genetic testing can inform future cancer screening needs of patients with non-metastatic prostate cancer.
3. The information is important to patients—they want to know how it may affect their family members now and in the future.
MSI-H=high levels of microsatellite instability
PARP=poly(adenosine diphosphate[ADP]–ribose) polymerase