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University of Michigan prostate cancer risk clinic may make ‘dramatic impact’ on disease burden, mortality
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The University of Michigan has opened a center designed to provide individualized, structured care for men with a genetic predisposition to prostate cancer.
The Prostate Cancer Risk Clinic — which opened in early March — emerged from research that elucidated the significant role that genetic mutations play in prostate cancer risk.
“Even though there are high-risk breast cancer clinics all over the country and all over the world, there are — as far as we know — no other clinics like this in the United States focused on prostate cancer risk,” Todd Morgan, MD, urological surgeon and associate professor of urology at Michigan Medicine, said in a press release. “No one else has turned the corner and said, ‘You know, wait a minute, men really need the same thing that’s already available for women.”
HemOnc Today spoke with Morgan about the need for the facility, how it will operate and the benefits he believes it will provide the men who enroll.
Question: Can you describe the need for this clinic?
Answer: In 2012, the US Preventive Services Task Force recommended against PSA screening for prostate cancer. It was controversial, and many of us think the recommendation went too far. For example, there really were not any caveats that accounted for men with a significant family history or other risk factors, such as race. Our effort is designed to identify men at high genetic risk for aggressive prostate cancer. We now understand that several genes that predispose individuals to certain cancers — such as BRCA1 and BRCA2, which are known to predispose women to breast and ovarian cancers — also predispose men to prostate cancer. BRCA2 mutations, in particular, put men at higher risk for an aggressive form of prostate cancer. The same is true of Lynch syndrome, which is known to predispose people to colon and other cancers. The list of genetic mutations that contribute to prostate cancer is growing, but the word is not out there. These men are at greater risk not just for prostate cancer, but for an aggressive form of it. That's the problem we are trying to address. We want to get these men into our screening clinic so we can identify their cancers earlier, when they are more likely to be treatable.
Q: How many men do you anticipate the clinic serving?
A: We estimate that we will have 200 to 300 men come in over the first 2 years. We expect most men will be referred from genetics clinics, as well as from high-risk breast cancer clinics where their sisters or mothers are maybe being seen for breast cancer risk. Because some of these women know they have mutations, our clinic now gives a clear reason for the men to get tested and then get referred in order to get involved in our screening program.
Q: Can you describe what participation in the clinic will entail?
A: It’s basically straightforward prostate cancer screening. These men are going to undergo a PSA blood test, a digital rectal exam and a urine test called SelectMDx (MDxHealth), which measures mRNA levels of the DLX1 and HOXC6 biomarkers. It’s basically a three-pronged approach. If any of the three components come back as abnormal, we will have a discussion with these men about the need for biopsy. If a man is diagnosed with prostate cancer, we will get him into our urologic oncology and radiation oncology clinics, as appropriate, and we will have further discussions about treatment options.
Q: How will payment work?
A: We anticipate that it will mostly be a mixture of insurance and modest copays. We are going to work with patients in advance to ensure preauthorization and, so far, we haven’t come across any issues.
Q: Is there a limit on how long men can participate in the clinic?
A: No. We are planning on this being relatively indefinite, although we anticipate stopping screening at approximately age 75.
Q: Can you describe the potential impact of this clinic?
A: Our overall goal has always been to make a dramatic impact on suffering and death from prostate cancer. We feel this clinic is the natural first step toward making a difference. The goal is to move from these initial 200 to 300 men in our clinic to the point where we are identifying early on which men have strong family histories of prostate, breast or ovarian cancers, and which ones need to screened for specific mutations across a broad population. We want to get to the point where we are not just targeting men with known mutations, but men who might be at considerable risk for genetic predisposition to prostate cancer. We feel that, over the next 5 years or so, there is a lot of room to expand the clinic to a broader at-risk population and make a bigger impact.
Q: Can you talk about the evolution of the understanding of genetic mutations and how they play a role in prostate cancer aggressiveness?
A: This has been an area of interest for decades, but it has taken a long time for data to show the extent to which these genes play a role in driving aggressive prostate cancer. One of the most important studies — conducted by Colin C. Pritchard, MD, PhD, and colleagues, and published last year in The New England Journal of Medicine — showed that 12% of men with metastatic prostate cancer have mutations in specific, important and targetable genes that predispose people to prostate cancer. These did not just include mutations in the tumors, but germline inherited defects or mutations in genes that affect DNA damage repair. There is significant evidence that shows patients with these mutations may be more responsive to certain classes of therapies, such as PARP inhibitors. What really stands out is that, if you look at men with localized prostate cancer, the percentage of patients with this same mutation in the germline is far lower. It suggests that those men who have localized prostate cancer and these mutations are much more likely to progress to more advanced forms of prostate cancer.
Q: Do you think the controversy surrounding the US Preventive Task Force’s recommendation about PSA testing makes a clinic like this more necessary?
A: Yes. There are some aspects of that report that are reasonable and evidence based. There is no question that, historically, too many men with low-risk prostate cancers were overtreated. Over the last five years, however, rates of prostate cancer diagnoses have plummeted 25% to 30%. Some low-risk prostate cancers are not being diagnosed, which may be OK because most men with those cancers likely are not going to die of their illness. However, high-risk prostate cancers also are going undiagnosed. This is the crux of the problem. By making a blanket recommendation against PSA screening, there naturally is going to be an increase in patients who are diagnosed with advanced prostate cancers that might have been avoided with PSA screening. We — all of us — need to do a better job finding the right men who need to be screened, screening the right way, and making management decisions that are in line with patients’ risks for dying of their disease.
Q: Do you envision this clinic being a model for other institutions?
A: Absolutely. There is a lot of excitement about the potential to identify men with heritable risk for prostate cancer. Experts around the country and around the globe are working on this. There is a big trial in England called the IMPACT study that has really pioneered this space. In many ways, we have looked to them in terms of the model for our clinic. We also have had discussions on this topic with experts at University of Washington and University of Utah. We hope to work with them and others to collaboratively gather data to better understand how we can broaden the scale of this idea. – by Kyle Doherty
References:
IMPACT Study Homepage. Available at: www.impact-study.co.uk/public/home. Accessed on March 22, 2017.
Pritchard CC, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1603144.
For more information:
Todd Morgan, MD, can be reached at UMH Urology, 1500 E. Medical Center Drive, Ann Arbor, MI 48109;email: tomorgan@med.umich.edu; Twitter: @wandering_gu.
Disclosure: Morgan reports research funding from MDxHealth and Myriad Genetics.