This is part of an ongoing series featuring interviews with physicians on topics related to hereditary cancer. This article was written by Kara Maxwell, MD, PhD. Dr. Maxwell is a physician scientist with the Basser Center and the Abramson Cancer Center at the University of Pennsylvania. Her areas of expertise are in cancer genetics, specifically in hereditary cancer syndromes.

In 2019, we hope that no man should die from prostate cancer. It’s a treatable disease with early screening and detection, but who to screen remains controversial. The United States Preventative Task Force (USPSTF) no longer recommends routine prostate-specific antigen (PSA) screening for all men and it is instead an individualized decision between a man and his healthcare provider. This is not unreasonable, given that many men may die with prostate cancer, not of prostate cancer, and there are significant concerns about complications from prostate cancer treatment. Therefore it is of paramount importance that we are screening and treating the men that need it most.

This is because, for some men, prostate cancer can be very aggressive. There are still thousands of men who die from prostate cancer each year, who may have benefited from PSA screening or targeted therapy. There seems to be a stage shift starting to occur, meaning that more men are being diagnosed with de novo metastatic cancer, which could be a result of doing less PSA screening. Metastatic prostate cancer is an incurable form of prostate cancer. As we know with mammography, mortality has decreased and there has also been a shift towards catching cancer in earlier, more treatable stages, with fewer women currently dying of metastatic breast cancer. However, just like with prostate cancer, there are concerns for over-screening, over-diagnosis, and over-treatment in breast cancer.  So, for both diseases, screening everyone is not the answer, but neither is screening no one.

As far as who should be screened, the USPSTF currently recommends considering a variety of factors, including family history, in a discussion of whether or not one should undergo PSA screening. African American ancestry is also very important, because more African American men get prostate cancer at younger ages and with more aggressive types of prostate cancer. In terms of family history, it’s well ingrained for providers to consider a family history of prostate cancer as raising a red flag, but a number of studies have shown that men may not also consider a family history of breast or ovarian cancer—and their providers may not be aware to ask. Often providers only ask about a history of prostate cancer when they’re trying to make a decision about whether or not PSA screening makes sense. I think it’s really important for men to recognize this connection—that mothers and sisters having breast and/or ovarian cancer should also be flags for men to discuss with their providers with regards to their decision to start PSA screening or not.

Differences in BRCA-Related Prostate Cancer
It is very important to identify men with BRCA mutations because BRCA-related prostate cancer is well known to be more aggressive, particularly with BRCA2 mutations. Studies have shown that BRCA2-related prostate cancer is more aggressive, more likely to be metastatic, and the men are more likely to die from their prostate cancer. In addition, I really want to stress that there still needs to be a lot of research on the different genes that are in play for hereditary prostate cancer, because it appears that they’re all a little bit different. For example, BRCA2-related prostate cancer may not necessarily be the same as HOXB13, BRCA1, CHEK2, or ATM-related prostate cancer.  There are also likely a lot of other genes that predispose to prostate cancer that we don’t yet know about.  And there is also a contribution from common single nucleotide polymorphisms called SNPs.

When and How to Screen
For a man with a family history of prostate cancer, but no BRCA mutation, it is recommended that screening should begin at age 45. For BRCA2 mutation carriers, prostate cancer screening should begin at age 40. However, this is also dependent on family history. If a man with or without a mutation has a family history of prostate cancer, where a relative had prostate cancer in their 40s, we would recommend he begin screening at the age 10 years younger than that family member was diagnosed. That’s rare, but it does happen. So for example, if a man’s father had genetic prostate cancer at age 40, his son would begin screening at age 30.

Screenings should occur yearly. Most men should recognize that they are going to have fluctuations in their PSA and that PSA screening, at some point, should wind up having to be more frequent if they’re following a trend upwards. In addition, screenings should not just be limited to a PSA, but should also include a digital rectal exam from a urologist.

The Issue of MRI Screenings
Whether or not a prostate MRI should be considered part of cancer screening is another important question. There are positives and negatives associated with this. Positives include that you might find prostate cancer at earlier stages than even a PSA. A digital rectal exam is effective, however if the cancer is on the other side of the prostate that can’t be felt, it’s not going to be detected. In addition, some very aggressive prostate cancers don’t make a lot of PSA–they de-differentiate and become less like run of the mill prostate cancer that can be detected by PSA screenings. The other major problem with PSA screening is that PSA can be elevated for a many different reasons besides just prostate cancer–so there’s this thought that maybe MRI would be a better way to screen.

The flipside with the MRI is that, unfortunately, prostate cancer treatment can have some difficult side effects for men. And so just like there are concerns with over-screening and mammography, there is an over-screening concern in prostate cancer. We’re not routinely recommending prostate MRI, because we don’t have any data to prove that it’s actually leading to benefit. Currently, MRI screening is not common and is primarily used in men who already have prostate cancer to further stage the disease.

Over-Screening Concerns
Why did we as a medical community decide to do less PSA screening? The major issue with prostate cancer treatment is that the side effects for men undergoing treatment can be detrimental from a quality of life standpoint. Prostatectomy, which is the surgical way of removing the prostate cancer, has a rate of erectile dysfunction afterwards. In addition, radiation can lead to erectile dysfunction, GI side effects, and urinary side effects.

As providers, we never want to treat someone for a prostate cancer that wouldn’t have caused any issues if it had remained indolent, but then have them experience side effects from the treatment that leads to significant detriment in their lives. Some people may feel that not having the cancer at all is the most important thing, but we can’t discount the issues that could happen when a man is on prostate cancer treatment and is having his testosterone suppressed. There can be a lot of difficult side effects and it can be very similar to going into surgical menopause.

The risks and benefits have to be weighed. This is why it’s even more important to understand the genetic risk factors, to gauge how aggressive the cancer might be. Men should be able to participate in that risk-benefit decision making process and decide whether they are willing to accept the risks if they know that their prostate cancer may be more aggressive.  We encourage all men to figure out their family history of cancers on both their father and mother’s side, in both their brothers and sisters. Discuss this history with your doctor to see if genetic testing might be warranted and for a broader discussion of what cancer screening might be right for you.