Genetic Testing’s Role In Prostate Cancer Care

“When a man has advanced prostate cancer, or a family history of prostate cancer, it’s considered standard of care now to do germline DNA testing,” Dr. Jeff Jones, a Professor of Urology at Baylor College of Medicine in Houston, tells SurvivorNet.

“We look at the mutation to see if there is a specific type of therapeutic agent that can be used in that particular patient, because they’re more vulnerable to having the targeted therapy. The cancer is more vulnerable to having it work in a more effective way if the mutation is present.”

What Is Germline Testing?

Germline testing analyzes DNA from a blood or saliva sample (normal cells) to find inherited mutations that raise cancer risk and may also guide treatment. In prostate cancer, recommended multigene panels typically include BRCA1, BRCA2, ATM, CHEK2, PALB2 and the mismatch-repair (MMR) genes MLH1, MSH2, MSH6, PMS2; additional genes can be added based on personal/family history.

“Germline means we’re testing the DNA within the white cells, typically, or the buccal mucosa, the lining of the inside of the mouth. We’re testing those cells for DNA mutations. And these are inheritable mutations, something that could be passed from one generation to the next, from father to son,” Dr. Jones explains.

“…When you have a family history, uncles, parents, grandparents, these are all men, of course, because it’s prostate cancer, then those individuals can pass on these inheritable genes, and so we look at the germ line to see if one of those genetic mutations is present, and they can they can help us determine sensitivity to types of therapy,” he adds.

Current guidelines recommend germline testing for all men with metastatic prostate cancer (when the disease has spread to other organs) and for those with high-risk or very high-risk localized disease or a strong family history. Your team may also suggest testing if you were diagnosed at a young age or have relatives with breast/ovarian, pancreatic, or colorectal cancers.

What Is Tumor DNA Testing?

As opposed to germline mutations, your cancer can acquire mutations that aren’t inherited. Tumor testing looks for DNA alterations and biomarkers that predict benefit from targeted drugs or immunotherapy. Two of the most clinically relevant signals in prostate cancer are DNA-repair defects, which could make the patient eligible for a PARP inhibitor, and markers of immune responsiveness like MSI-H/dMMR and tumor mutational burden, which show the number of mutations you harbor (the higher the number of mutations, the higher responsiveness to the immune system).

“[We] look at tumor mutational burden and we look at specific genes that are mutated in that tumor,” Dr. Jones explains. “And these are not inheritable. These are something that happens sporadically, often. They could be environmentally induced, or some other exposure that has created this, or it could be a spontaneous mutation that happened in that individual, but it’s not passed on from generation to generation.”

Questions To Ask Your Doctor

• How do I know if my cancer is inheritable or not?
• Should I be tested for DNA mutations?
• Should my family members be tested?
• If I have a DNA mutation, does it mean that I have a worse prognosis?
• What, if any, targeted treatments are available to me?

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