Interview with Dr. Matthew Cooperberg: New Genomic Test Helps Guide Treatment for Prostate Cancer

Audio Interview

Targeting treatment for prostate cancer — Hear an interview with Dr. Matthew Cooperberg, a urologist and an expert in prostate surgery.

Are We Overtreating Prostate Cancer?

Andrew Schorr:

In the next year, more than a quarter of a million men in the U.S. will be diagnosed with prostate cancer. Of these, who can be watched? Who needs treatment? Which men need aggressive treatment? Well, there's a new genetic test to help guide us in decision making. We'll hear more about that from a leading expert from UCSF Medical Center. It's all next on Patient Power.

Hello, and welcome to Patient Power, sponsored by UCSF Medical Center. I'm Andrew Schorr.

Well, as we mentioned, about a quarter million men in the in the U.S. will be diagnosed with prostate cancer, men who are my age, I'm 62, and some are younger, some are older. And we say, well, gee, we've all heard that men die with prostate cancer but not always from it, so who needs treatment? Who can have, what we call, active surveillance? Who, maybe, should have a prostatectomy? Who should have, maybe, more aggressive therapy? And, of course, with prostatectomy, can go complications, like erectile dysfunction, incontinence, other issues.

Have we been overtreating prostate cancer? The urology community says we probably have, and some men will say we probably have. What do we do to correct that? Can we look at genetic changes and see which men can be followed, which men need more aggressive care?

Well, a leader in the field is with us right now, and he's from UCSF Medical Center. That's Dr. Matthew Cooperberg, who is associate professor in urology, also epidemiology and biostatistics. And at the 2013 meeting of the American Urological Association, he presented new study data on genomic testing to help us get the guidance we want in prostate cancer. Dr. Cooperberg, welcome to Patient Power.

Dr. Matthew Cooperberg:

Thank you very much.

Andrew Schorr:

All right. Did I set the problem out right, that maybe we've been overtreating some men, and some men we need to identify with aggressive prostate cancer? We could do a better job there, too?

Dr. Matthew Cooperberg:

I think you set it up perfectly. If you look at the disease pattern, the epidemiology of prostate cancer, since we've started PSA screening in the 1990s we have dropped the cancer death rate, for this disease, over 40 percent. It's been a tremendous success, many, many thousands of lives saved. But the price of that has been high. There have been many thousands of men, on the other hand, who have undergone surgery, radiation therapy, and other treatments, that they did not need for low risk prostate cancers, that they never would have known they had, had we not started checking PSAs, and doing biopsies, and that sort of thing.

That's the route of this ongoing prostate cancer controversy. As many will have heard, the U.S. Preventative Services Task Force decided that the solution to the problem is to simply stop screening for prostate cancer altogether and roll the clock back to the 1980s. Most of us argue that that would be a disaster, and really reflects a very poor understanding of the disease.

There is no question, though, that we need to do a much better job targeting treatments to the men who are most likely to benefit from them, and these new emerging genomic tests, which look at gene expression in the actual prostate tissue, we think, are going to be one piece of the solution, in terms of helping men make better decisions, and make decisions for treatments, which are more appropriately targeted for their individual situations.

Emerging Prostate Cancer Tests

Andrew Schorr:

Okay. Tell us about the study you presented at the AUA meeting, and what the results were, and what we can learn from that.

Dr. Matthew Cooperberg:

Sure. So this study focused on one of a number of emerging tests. The one that we focused on in this study was from Genomic Health, which is a company here in California, which is probably best known for the Oncotype DX breast assay, which has been on the market for a number of years, and, which helps women with breast cancer decide whether or not they need to get chemotherapy. They've had a colon cancer assay on the market for a few years, as well, and have now been developing an assay for prostate cancer.

And all of these tests look at the expression levels of genes, in other words, looking at which genes are relatively turned on and turned off, in the actual cancer tissue. The specific challenges with prostate cancer are, number one, the disease tends to be heterogeneous, so you can have areas of more aggressive, and less aggressive cancer, within an individual prostate, and also that prostate biopsies are very small. It’s taken time to really miniaturize the technology, to the point where they can work with very small amounts of tissue.

The original development studies, on this assay, were done at the Cleveland Clinic over the past several years, and what we presented was the first major validation study proving that this can, actually, work in the real world in contemporary practice. And the question that we intended to answer here is whether the test can help us predict the true nature of prostate cancer from biopsy tissue.

One of the problems, and one of the reasons that we tend to overtreat low risk disease is, we know when we see a high PSA, and do a prostate biopsy, we may find what looks like a low risk prostate cancer. So it will be low grade, low Gleason grade. There may not be very much cancer. There's no sign of cancer outside the edge of the prostate, etc. However, we know, in somewhere between 25 and 35 percent of cases, if we then went ahead and removed the prostate, in a case that looked low grade, we will actually see something worse than what we expected, higher grade disease, higher stage disease, some more cancer than we expected.

This uncertainty, the knowledge that we may have undersampled the cancer, is a source of great anxiety for both patients and doctors. And it's one factor, certainly not the only factor, but it's one factor that tends to drive men, with low risk disease, toward overtreatment, toward treatment that they did not necessarily need.

So the goal with this study was to see whether we could use this test, the Oncotype DX prostate test, which they're calling the GPS test, to actually improve our predictions of what the actual nature of the cancer is. And one of the challenges here, too, is that we can actually do a reasonably good job at that prediction with standard clinical information. With the PSA level, with the number of biopsy cores that have cancer in them, with the Gleason grade, our accuracy is in the 70 to 80 percent in making these predictions. The bar is actually pretty high to do better.

What we looked at is a large cohort of men who had what looked like low risk or low-to-intermediate risk disease at UCSF, over the past several years, who went on to surgery, so we know the true pathology. We looked at over 400 men and ran this GPS assay on the tissue and found that, in fact, it does give us independent information. There is a signal in the genes that does give us information, above and beyond what we can determine from the standard factors like the PSA and the Gleason score, in terms of predicting the true nature of the cancer.

Andrew Schorr:

Hmm, okay. Let me see if I've got that right. So you have done pretty well with the constellation of diagnostic tools you have now, but there's still the fear that some men were overtreated, or you thought it would be low risk, but it turned out to be high risk, and men worry about that, so they say, Go for the gusto and remove my prostate, because I don't want to worry.

Now you look at this tissue, and you find that if you did that on newly diagnosed patients that, looking at the genetic changes, that you could have a pretty high batting average.

Dr. Matthew Cooperberg:

Exactly. That we can improve the accuracy of predicting the true pathology, and, therefore, we can improve the confidence in which we can tell an individual man that he has truly low risk, low grade prostate cancer, which is unlikely to be a clinical problem in the short to intermediate term, at least.

Prostate Cancer Active Surveillance

Andrew Schorr:

And you can avoid surgery at this time.

Dr. Matthew Cooperberg:

Well, that's the idea. So we've been doing active surveillance for a number of years, and what that means is, not go home and forget about this, but it means that this is a low risk cancer that we can safely watch with regular PSA checks, with repeat biopsies every couple of years, and that if there's any sign of the cancer progressing, we can treat it at that point with every expectation of curing it. Our hope is that we'll be able to give men a better sense of the likelihood that they will do well on surveillance, that the cancer will not progress and will not need treatment.

Andrew Schorr:

Let's talk about that for a minute. So if I walked in and there was a suspicion that I might have prostate cancer, and you do the genetic test—and that comes from biopsy samples. Is that right?

Dr. Matthew Cooperberg:

That comes from biopsy. Right. We wouldn't run the test until we knew that you had a cancer diagnosis.

Andrew Schorr:

Okay. So I have a cancer diagnosis. The question is can I be watched or do I need some level of more aggressive treatment, surgery or radiation, etc. Okay. And you have a test now that you think is validated, and goes over that higher bar you talked about, but it's not perfect. So I still have a worry. You all say to me, Well, Mr. Schorr, we don't think we need to do anything now. But do I just go home or, as you say, I'm going to come back to you from time to time and we're going to revisit?

Dr. Matthew Cooperberg:

Absolutely. The older concept was watchful waiting, which really applied to older men, men with a lot of other medical problems, where messaging was, Well, if you've got prostate cancer it's probably not going to be a problem for you. Go home and don't worry about this. If it progresses later, and you develop symptoms, we can treat it at that point. We can't cure it, but we can treat it with hormonal therapy and other things like that.

Active surveillance says that this looks to be a low risk indolent prostate cancer, meaning one that is likely not to progress. We don't know that for sure, but our expectation is that, even if it does need to be treated at some point, the window of opportunity for cure is probably measurable in years if not in decades, and that even if men may eventually need some intervention it does not need to be done today.

And in the meantime, and this is particularly relevant for younger men, in the meantime they can avoid the potential side effects of surgery, radiation therapy, etc., which may impact them for a long time, if they do have one of those events after treatment.

Precision Medicine

Andrew Schorr:

It sounds like we're getting into the era, we hope, of precision medicine in the treatment of prostate cancer and that this is a big step forward.

Dr. Matthew Cooperberg:

Absolutely. This is precision medicine. The goal is really drilling down to treat every individual as an individual and recognize that every tumor is unique. And the fact of the matter is, we actually do a lot of harm, just in our language, in many cases, specifically in oncology, because we use the word cancer for a lot of things in biology, a lot of things in life. And, at one end of the spectrum, you've got very aggressive cancers, like pancreatic cancer, that really are lethal in months or a small number of years. Prostate cancer is at the far other end of the spectrum.

And then, even within prostate cancer, there's a huge range of aggressiveness in biology ranging from very aggressive cancers, which kill most men eventually, even though it's still slower than things like pancreatic cancer, but at the other end you've got many, many men who have, basically, a few abnormal looking cells in the prostate, that would never grow had we never found them. But once the word is out there, once the word cancer is, kind of out there in the air, for many men it’s hard to avoid an inevitable road to treatment.

These tests are not the end of the story, because, A, for one thing they are still not a hundred percent accurate. They improve the accuracy of risk verification, but they're certainly not perfect. And they're also not a yes and no. You get a continuous score that's another piece of information that can help the doctor, and the patient, come to a decision. But it's not like a pregnancy test with a plus minus, take it in, leave it, leave it in, take it out, and we're never going to have something that's that concrete, that black and white.

The decisions are always going to be made under some degree of uncertainty, but the hope is that we can reduce that uncertainty progressively and help men, again, make better decisions and have better confidence in their decisions, and, hopefully, better satisfaction with the ultimate outcomes.

Andrew Schorr:

You've been researching this for a while, and you have had men, where you've talked to them about the results of this test. Do they seem relieved when you give them this sort of state of the art type data, and it's part of the discussion.

Dr. Matthew Cooperberg:

Well, that's a great question. How we actually use these in clinic is a big unknown. The research study, that I just described, was all done retrospectively on tumors that were sitting in our archive and the patients, in this study, were never really given the result, because it's still investigational. The test has just now been on the market for about a month, and there's other tests like it that have been on the market, maybe, six to eight months, and how exactly we should be using these in practice, is really the subject of a lot of ongoing investigation.

We actually have a large grant from the Department of Defense to look at exactly that, how really to bring these to optimal use in clinic. I think, from anecdotal experience so far, yeah, in cases where we're, sort of, on the fence, as to whether a man should get immediate treatment, or should go on active surveillance, there is value. I think when we run one of these tests, and the score comes out low, it's another piece of reassuring data that there's not an emergency here, there's no urgency for treatment. On the other hand, if the score is high, that would be the sign that, Look, this may be a tumor that has been undersampled and should be treated more aggressively.

And I do think the patients appreciate the sense this is personalized. This really is precision medicine. It is looking at their individual tumor, their individual tumor's genetic predilections.

Closing Thoughts

Andrew Schorr:

Well, I want to compliment you for all the dedication of the team there at UCSF, because I know you've led the way as a center in investigating and treating prostate cancer. And I get the sense, there's a lot of passion that I'm hearing in you, that this, in urology, is the kind of tool that can make a big difference.

Dr. Matthew Cooperberg:

Absolutely. Absolutely. It's honestly very frustrating, from where we sit, to watch this ongoing controversy unfold in the media, about, should we be screening, should we not be screening, should we stop treating altogether. There's really no question that the correct answer is, of course, somewhere in the middle. We shouldn't stop screening wholesale. On the other hand, we cannot continue to overtreat low risk prostate cancer. The correct answer clearly is, to screen, to screen the right men and really to focus on high risk prostate cancer, to focus treatment efforts on those men who are at risk of dying of it.

We can't forget that even though it's a small minority of the men with prostate cancer, men with high risk disease, which still kills more men than any cancer except lung cancer in the US. And even though the numbers are falling, our job is certainly not finished. And those are the men for whom the screening efforts are intended, and if we can pull back, and avoid overtreatment of low risk disease, then the controversy really should dissolve.

Andrew Schorr:

Well, we wish you all the best. Thank you for explaining this to us and for your leadership in the research. Dr. Matthew Cooperberg from UCSF Medical Center, and all your work in urology, thank you for being with us on Patient Power.

Dr. Matthew Cooperberg:

Thanks very much.

Andrew Schorr:

Great news, I think, as we push things forward in prostate cancer and try, and maybe we've arrived now, as he said, in the era of precision medicine so you, the man facing prostate cancer, get the treatment that's right for you.

Thank you for being with us. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.

Recorded on: July 9, 2013


Reviewed by health care specialists at UCSF Medical Center.

This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.

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