BERKELEY, CA (UroToday.com) - Genetic tests have been developed for a multitude of diseases and conditions, and more new tests continue to be introduced for use in the clinical setting. A growing number of tests are being developed to look at multiple genes that may increase or decrease a person’s risk of common diseases such as cancer or diabetes. Such tests and other applications of genomic technologies have the potential to help prevent common disease and improve the health of individuals and populations. For example, predictive gene tests may be used to help determine the risk of developing common diseases, and pharmacogenetic tests may be used to help identify genetic variations that can influence a person’s response to medicines.
We recently spoke with Stephen J. Freedland, MD and associate professor of surgery and associate professor in pathology at Duke University Medical Center in Durham, NC USA and he provided some insights into current and future applications of genetic testing as it relates to prostate cancer and the decision-making process for active surveillance vs treatment.
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Q: Coming off five days at the AUA where there has been a lot of focus on genomics and the new PCa detection guidelines, where are we now with genomics and how does genomics fit in with the new guidelines?
A: Genomics is a very promising area and basically the idea is to help us identify who to treat and who not to treat. And among the patients we want to treat, it can help give us an idea of who has aggressive disease that we need to treat with multimodal therapy.
I actually served on the PSA guideline panel and if you read the text, it is clear that we cannot, in the U.S., in 2013, separate diagnosis from treatment, so the only way currently to curtail over-treatment is to curtail over-diagnosis. Many people recognize that the future is in molecular markers, of which genomics looks very promising. However, there will be other biochemical protein type markers, in which case, over diagnosis would be acceptable because we can separate out who to treat and who not to treat and really embrace active surveillance. Currently, we have a room full of people saying that they have many of their patients on active surveillance, but the data suggest that the percent of men who receive active surveillance is in the single digits. The AUA guidelines were driven by our current practice patterns and molecular markers/genomics in general hold tremendous promise to help us separate those two conditions, over-detection and over-treatment.
There have been many companies at this meeting that have presented some very exciting data. On a certain level, probably all of them have prognostic value, but at this point it is difficult to declare a winner as the story is not yet finished being written. The studies they chose to do and the data coming out of these studies will drive which test we ultimately chose to use in clinical practice in the future.
Q: Based on the technologies and tests available today, would you feel comfortable using one or more of them and rely on the results to decide if you should treat or not treat your patient?
A: These tests certainly can add prognostic value. I don’t think you can take a high-risk patient and tell me it is safe not to treat. If anything, it can improve risk stratification and prediction, but they are not 100% accurate. It can’t tell me with 100% certainty whom not to treat but it can help improve my confidence about doing active surveillance (AS). Many in the academic community have embraced AS and I do feel comfortable doing AS; right now about 20-30% of my patients are going on AS. I am not going to stand up and say every low-risk patient is going on AS because that is not the reality, but 20-30% of all-comers.
For someone who tries to get a comfort level with AS, these tests can be extremely helpful. But it is not only for AS, but also for intermediate-risk patients, it will help guide me - should I add hormone therapy, or not, to a patient choosing radiation? For intermediate-risk patients after surgery - should I add radiation or not? It is not just for AS patients, it also helps deciding if I should add one or more treatments and what steps should be next.
Q: What do you think happens down the line, 2-3 years from now, would it change the treatment algorithm for prostate cancer?
A: I can definitely see a day, I am not sure it will be 2-3 years from now but 4-5 years down the line, where we do a PSA test, and if that is abnormal, we do a confirmatory blood or urine molecular/genomic test before preceding to the biopsy. For high-risk men, we go to biopsy and then we subject the biopsy to genomics, and based on that we present the treatment options. If the tumor looks good, you push more towards AS, and if the tumor looks bad, you push towards treatment. There is no test being used routinely today, but there are a lot of companies now in this space with tests that are looking very promising. They are still doing research and some of them are presenting here at the AUA. While there is certainly more work to be done, some of the early data certainly looks promising.
Q: Looking at it today, are these tests ready for “prime-time” yet?
A: There are several commercially available tests right now, but at this point I do not think that is something you would do for every patient. There are select patients where it is appropriate to use these tests. Like any new test, the physicians in the field need to start to develop a comfort level using the test. The tests are not so overwhelmingly amazing yet that we will go from never using them to using them in every patient – at least not overnight. There will be a ramp-up period where we will start getting comfortable using the tests and we will start to develop and rely on our own anecdotal experience. Unfortunately, for many physicians, their own anecdotal experience trumps the literature: “I had a patient with low-risk disease and I did this test and it told me it was high-risk disease and I operated and it turned out not to be bad disease and I will never use the test again.”
There will always be misclassifications with any tests so you cannot give up a test based on n=1. While that is problematic -- and what I think that many clinicians may do -- I think with continued studies by the companies, ultimately may people will come around to using the tests. Ultimately it will be interesting to see how these tests work in the real world. It took a while for PSA to catch on, so it will take some time here, too.
Q: Do you think the urology community overall is ready to embrace these test/genomics based on their knowledge and understanding, or do you think they need more education?
A: I think they are anxious for a test like this, they are ready to be taught but I don’t think they necessarily know how to use them. I think we have gone from no test to, I don’t want to say too many tests, but I want to say a lot of tests, which can lead to confusion, and many of the tests have very similar names so it can certainly lead to confusion. I even hear people get confused between PSA and PCA3, not as much urologists, but non-urologists will get those confused. So I think the urologists are anxious to learn, but there are challenges as far as reimbursement and how to pay for it. It is not a simple blood test that costs $20 and insurance will guarantee they will pay for it. These are new molecular genetic tests that cost a fair amount of money and you can argue that if you can avoid treating somebody unnecessarily, it is certainly worth the money. I am not saying they are not cost-effective but they are not cheap tests. Will insurance cover them? If they don’t, will the patient be liable for paying the cost? Is the practice going to be liable? It is a little bit trickier than putting a checkmark in a box to add the PSA test. I think some of that is going to take some time to sort out.
Q: Do you think there is a big difference between academics and private practice as far as level of acceptance and level of uptake and understanding of the area of genomics?
A: I think, by our nature, academics are a little more skeptical, which is what they teach us to question everything. So I could see this having a much better uptake in the community, at least initially. I do think, when you look at models of other diseases and biomarkers, it takes a few key opinion leaders from the academic world who really become spokespeople for this. That is either paid promotional speaking or un-paid, peer-reviewed presentation of literature, promoting something they really believe is better patient care, something they really believe is going to be better for the patient. Important for these companies is that they don’t do just one study that they think will answer every question, and then they start marketing and send the sales reps out in the community to start selling this. A lot more research needs to be done and it needs to be done in partnership with academics. However, I do think it will take off quicker in the community.
We have gone from zero tests available to half a dozen tests available in just a couple of years and it gets to be a very crowded market space very quickly. Some of the companies jumping into this area are very small and very focused on this particular therapeutic area; others are very big companies and well known outside the prostate cancer market. Molecular tests for breast cancer have been available for 10 years, and these companies have become the dominant leaders in the field, and they are now moving into the prostate cancer market. These are not only small biotech companies, but also are bigger companies who have a very clear vision of a business plan and a proven success.
Some companies have done more studies than others and have a solid business plan of where they are going. On a theoretical level, all the signals work and they probably work well. One company may have done more studies and have more data to support it, but on a biological level, they are probably all going to work well.
It will be very interesting to see how all of this plays out.
Click HERE to view a poster related to this interview
Click HERE to read a related commentary by Stephen J. Freedland, MD
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Stephen J. Freedland, MD is associate professor of surgery and associate professor in pathology in the Department of Urology at Duke University Medical Center in Durham, NC USA.
He received his MD degree at the University of California–Davis School of Medicine, and went on to complete residencies (in general surgery and urology) at the University of California–Los Angeles Medical Center and a fellowship in urologic oncology at Johns Hopkins Hospital.
His clinical interests include prostate cancer; benign prostatic hyperplasia, and other prostate diseases; GreenLight laser prostatectomy; radical prostatectomy; and TURP.
His research focuses on prostate cancer, obesity, nutrition, diet, PSA, biomarkers, and statistical modeling.
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The interview was conducted by Anna Forsberg, medical director for UroToday.com. Anna received a BSc in zoology from Louisiana State University, and a BSc in biomedicine and MSc in clinical drug development from Uppsala University in Sweden. She has worked almost 20 years in the global pharmaceutical and medical device world, involved with clinical research management and as a Medical Science Liaison (MSL) before joining UroToday as Medical Director. Her focus in clinical research and as a MSL has mainly been in the fields of urology and oncology.
