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Understanding prostate cancer, the most common cancer in American men

Peter Levonian

“You don’t want to do prostate cancer screening” says my primary care provider. “After all, you don’t die from prostate cancer; you die with prostate cancer.”

This occurred as part of an important conversation that men-of-a-certain-age need to have with their primary care providers. His counsel (actually, strong opinion!) was well-intentioned but not wholly accurate. Historically, prostate cancer screening was recommended starting at the age of 50 years. This involves an annual blood test and annual digital rectal examination. The blood test measures a chemical in the blood called prostate-specific antigen, or PSA. This approach to screening in the general population came under some criticism in the last couple of decades. The issue raised is that prostate cancer tends to be fairly indolent. Although prostate cancer is the most common cancer in American men, it generally does not behave badly. In other words, most men with prostate cancer survive the disease and have the opportunity to die from something else. In many cases, it may be that men will survive the disease even without aggressive treatment. The treatment for prostate cancer can leave men with some undesired side effects, including changes to urination and erectile dysfunction. As a patient once posed to me, “Why would I want to be screened for a disease that may not kill me, but the treatment might make me wish I was dead?”

Here’s the problem: Some prostate cancers behave very badly and are very aggressive. There is a substantial risk of death from aggressive prostate cancers. The aggressiveness of prostate cancer is most often determined in the pathology department through multiple measures of a biopsy in a scoring system, called the Gleason score. A Gleason score of 7–8 or higher is considered an aggressive form of prostate cancer. So, how do we know which men are at risk for high Gleason prostate cancer?

It turns out, family history can be an important guide. Predictably, family history of aggressive prostate cancer or multiple relatives with prostate cancer under age 60 can be important indicators. However, what is often missed is that family history of other cancers can also be very important. If a person has a family history of ovarian cancer, pancreatic cancer, or early age breast cancer, this can be a sign of an underlying genetic susceptibility to cancer, including prostate cancer. A study from 2016 looked at about 700 men with aggressive prostate cancer and found genetic mutations in about 12% of these men. There were mutations in BRCA1, BRCA2, ATM, RAD51D, PALB2 and CHEK2. Within this alphabet-soup of gene names, several may be familiar. In fact, these are all hereditary cancer risk genes that cause an elevated risk for breast cancer and other cancers, in addition to the risk for aggressive prostate cancer. Again, here was a group of men who were studied only because of their own history of advanced prostate cancer. The finding that a number of these men have inherited gene mutations in cancer risk genes is critical information for a family to know. Knowing about these mutations in men with prostate cancer can be invaluable to understanding the risk for breast and other cancers in their sisters and daughters.

The other side of this coin is also true: Men should not ignore news of a breast cancer risk gene in the family. I work with families who are at inherited risk for cancer. Genetic testing will occasionally detect mutations in the BRCA1 or BRCA2 genes. This finding tells us that all close relatives are at a 50% chance of having the same gene mutation. I have had a number of brothers and sons tell me “that’s only important to the ladies in the family.” Now we know better. This should be important to the men as well because mutations in some genes will confer a risk for aggressive prostate cancer in men or pose a risk of cancer that can occur in either gender.

Understanding who is at risk for cancer — whether prostate cancer or other cancers — begins with an understanding of the family history. Talk. Research your family medical history. If there is any worrisome family history, consider seeing a genetic counselor and proceeding with a genetic test of multiple hereditary cancer genes. You could end up learning information that could save lives in your family. Perhaps your own.

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