The PSA test measures blood levels of a protein made by the prostate. Levels of less than 4.0 (nanograms of protein per milliliter of blood) are usually considered within the normal range, while levels of greater than 4.0 are said to show an increased risk for prostate cancer. But the study found that 15 percent of the men who had “normal” PSA levels still had prostate cancer. High-grade cancer was found in about 2.3 percent of those so-called “normal” men. It appears that the lower the PSA level, the smaller the risk–the likelihood of having cancer rises as PSA levels rise. But there is no clear PSA level at which a person can be guaranteed cancer-free. Some incidence of high-grade cancer–the most aggressive–was found at every PSA level.
The study’s results are unsettling. How do men with PSA levels that are typically considered normal decide when they need a biopsy, the next step in diagnosis? When evidence of cancer is discovered, what is the best course of action? Should every case of prostate cancer be treated? NEWSWEEK’s Laura Fording asked Dr. Ian Thompson, chief of urology at the University of Texas Health Science Center at San Antonio and lead investigator in the study to weigh in.
NEWSWEEK: How many men will be diagnosed with prostate cancer in their lifetime?
Dr. Ian Thompson: A man in the United States has a 17 percent risk of being diagnosed with prostate cancer in his lifetime–and a man’s risk of dying of prostate cancer is 3 percent. That means somewhere around 200,000 men each year are diagnosed and about 30,000 men die each year from the disease.
Is the incidence of prostate cancer on the rise?
When PSA as a test for screening for prostate cancer came into place, it identified a lot more people, so incidence went up in the late 1980s and early 1990s. Since then, it has come back down to a steady rate.
What causes prostate cancer?
The only two things I know are: one, I don’t know the answer to that, and two, it’s very complex.
Your study found that 15 percent of men with “normal” PSA screening results had prostate cancer. Does that mean that PSA testing is flawed?
Previously, PSA was thought to be a positive or negative test. It was thought that men with a PSA above 4.0 were at risk for prostate cancer and should be recommended to go for further diagnostic testing, specifically, a prostate biopsy. Men with a PSA of less than 4.0 were thought to be at such a low risk for prostate cancer that they could just be examined on a periodic basis. Our data show that there is a measurable, and some might say a substantial, risk of prostate cancer in men with a normal PSA. That includes risky aggressive prostate cancers.
Does that mean that the cutoff point on the PSA test–the point at which men are deemed at no risk for cancer–should be lowered?
It means that the PSA test should be looked at differently. There is a table in the [study] that shows the risk at a given level of PSA. For example, a man with a PSA of between 3.0 and 4.0 has about a 27 percent risk of having prostate cancer if a biopsy is performed. Of those men, about a quarter will have aggressive prostate cancer–about a 7 percent risk of aggressive prostate cancer in men with a PSA of 3.0. On the other hand, the risk of aggressive prostate cancer in the man with a PSA of 1.0 is only about 1 percent. So men with what we thought was a normal PSA can [by understanding the risks associated with each PSA level] make a more informed decision about whether not they should have a biopsy. There are men who are at higher risk: African-American men, older men, men with a strong family history of prostate cancer. Say, for example, that a man with a PSA of 3.0 has a family history of prostate cancer. His risk is probably going to be higher than 27 percent. The new data allow men to better individualize decision-making.
If a man has a PSA level of 3.0 and absolutely no other symptoms of prostate cancer, except he had a family history of prostate cancer, should he consider having a biopsy?
It’s been shown time and time again that the vast majority of men who are diagnosed with prostate cancer because of symptoms already have metastatic disease.
So is PSA screening still a good diagnostic tool?
This study does not address whether screening is good or bad. There is a debate over whether PSA screening should or should not be done. At this point in time we do not know for sure that having PSA screening actually reduces a man’s risk of dying from prostate cancer.
But why wouldn’t screening reduce the risk?
We know PSA screening finds cancer early. But does screening find cancers that are destined to cause death? One of the possibilities–and we don’t know for sure–is that screening may find slower growing cancers that may pose no risk and may miss faster growing cancers that do pose risk. For example between 50 and 75 percent of men in the United States have had a PSA test in the past five years, but prostate cancer death rates [have fallen only marginally]. So screening by itself probably can’t prevent all prostate cancer deaths. There is a real problem in screening if you find a cancer that is not going to cause a man a problem in his lifetime and then treat that man for that cancer and he ends up having side effects from the treatments. That means all those side effects and all of the costs associated with treatment were unnecessary. This study says that a man should look at our data and say, “I should look at my risk based on my PSA and other risk factors, think about my own priorities and perhaps consider investigating whether I have prostate cancer before my PSA [level] gets to 4.0.”
Some experts are worried that the results of this study will encourage more men with what have been considered normal PSA levels to get biopsies, and if cancer is found, it will be unclear how to treat it. In other words, more men will be treated unnecessarily.
That’s certainly a possibility. There is a trade off. There will be a number of men with intermediate to lower-grade cancers that will be found at these lower PSA levels. The trade-off here is that you may find some of those high-grade cancers that you may otherwise have missed, but you will find other cancers that may be lower risk. One collective approach is for those men with lower-grade cancers at low PSAs to think about the concept of watching the cancer, it’s called watchful waiting. One of the observations that this study makes is that watchful waiting should be a component in the practice of management of prostate cancer.
But how many people are actually going to do that?
Less than probably should, but I think that this observation should reinvigorate the discussion with patients about watchful waiting as an option.
Is having a biopsy a complicated procedure?
It’s an outpatient procedure. In most cases it should take under 15 minutes or so. It’s done with ultrasound guidance; there’s a probe that’s placed in the rectum that images the prostate using ultrasound. That probe guides a fairly small needle. Generally speaking, between 6 and 12 small cores are removed from the prostate, then the man goes home or goes back to work or whatever. There are risks of bleeding or infection, but both of those are quite unusual.
Does having a biopsy affect prostate function?
No.
Does a biopsy always find the cancer, even if the cancer is very small?
No.
How do doctors differentiate between more and less aggressive versions of prostate cancer?
There are ways we do it, but those ways are imperfect. We tend to use a combination of PSA, because there is no question that when PSA goes sky-high, like in the 100s, that the cancer is probably outside the prostate. The way the prostate feels, if you can feel the cancer outside the prostate, that’s a bad sign. But most prostate cancers detected today in men who are being screened are confined to the prostate. In those men, the main way we can tell something about the aggressiveness of the cancer is the by Gleason score, or the grade: the appearance of the cancer under the microscope. That can run from a number of 2 to a number of 10–10 being the most aggressive, 2 being the least. Virtually all prostate cancers today, the very low grades, the 2’s, 3’s, and 4’s, are almost nonexistent. Virtually all run from about 5 to 10.
Could someone with a grade 5 be left untreated and possibly never have a problem?
Yes. It’s also a possibility for a grade 6. But this is imperfect. For example, there are almost certainly high-grade prostate cancers that, in an individual, will not cause that man harm if left untreated. The flip side is there are Gleason 5’s and Gleason 6’s that, in an individual, over a period of time, can spread and kill a man. The real challenge, which needs investigation and research, is how to distinguish the cancer in the man that needs to be treated from the cancer in the man that will never cause problems. It involves both characteristics of the cancer and characteristics of the man. An elderly man with multiple problems may have low risk [with] an aggressive cancer. But for a young man with a slow-growing prostate cancer, that cancer may cause him risk. At this point in time we simply do not have a reliable way to identify which individual cancer in which individual patient must be treated.
Do you treat them all, then?
No. But there is a culture in the United States toward treatment. It’s a culture in the medical community, it’s a culture in society, as well. We, as a society, tend to do more medical treatment for everything than other societies do. So it’s not surprising that about 90 percent of men with prostate cancer, given all the options–and I suspect that many of them are told that watchful waiting is an option–opt for treatment.
Are there any other methods of diagnosis in the works other than PSA screening?
You bet. I’m in a meeting right now in Washington, D.C. discussing that very subject. My personal opinion is that the diagnosis of prostate cancer will include an integration of factors: constitutional factors, such as family history and so forth; behavioral factors such as diet, use of supplements, exercise, caloric intake and so forth, and tumor factors: features of the individual cancer. It’s probably going to be a combination of all of those items together that will yield the best screening test. Of ongoing studies, one study [is being done by the] Early Detection Research Network of the National Cancer Institute. It is examining protein profiling, which means instead of looking at PSA, which is one protein, it looks at thousands of proteins simultaneously. That’s just one approach. In San Antonio [at University of Texas Health Science Center], we are looking at combining that approach along with genetic and dietary risk factors and behavioral risk factors to create an algorithm or a computer program that determines risk. There may be a holy grail out there–some blood test we haven’t found yet. But for most cancers thus far, we haven’t found that.
Is there anything a person can do to reduce their risk of getting prostate cancer?
The only thing that we know of, short of being born female, is taking Proscar. Proscar is a drug that is used to treat the symptoms of enlargement of the prostate. It blocks the conversion of testosterone to a more potent hormone called dihydrotestosterone–a conversion that occurs in the prostate. So it lowers the male hormone levels in the prostate. It actually causes the prostate to shrink. It reduces the risk of developing prostate cancer by 25 percent. [Dr. Thompson was the lead researcher for a prostate-cancer prevention trial involving the drug Proscar last summer.]
Do you think totally healthy men should consider taking Proscar?
It depends. There are risks and benefits. There is obviously a cost associated with it. It can cause some sexual problems in a minority of men. Those symptoms tend to go away if the man stops taking it. It also can affect the kind of prostate cancer that develops. It either affects our ability to grade the prostate cancer or in some men it may actually cause a more aggressive prostate cancer. That appears to be a minority, as compared to the 25 percent reduction in risk. But because it’s such a complex issue, a man who is concerned about his risk should have a discussion with his physician. It is not a simple discussion, and he needs to speak with a physician who understand the complexity of it and who’s an expert in the specifics.
Is there anything dietary that men can do to reduce their risk of prostate cancer?
Do you want things that are proven?
Yes.
None. The public loves to do all sorts of things hoping that they’ll work. And there are epidemiologic data that would suggest that dietary things, perhaps exercise, perhaps losing weight, stuff with regard to lycopene, selenium, vitamin E, reducing dietary fat, reducing calories. There are thousands of observations that have been made epidemiologically. All are hypotheses; all are unproven. And when you test these kinds of hypotheses, frequently you find out that you’re wrong. An example of this is estrogen replacement. All of those epidemiologic observations that we made, and all of those women who took estrogen-replacement therapy indeed may have harmed themselves. Some approaches more than likely reduce the risk of disease. For example, reduction of caloric intake, increases in number of vegetables one eats, those things probably reduce your risk of heart disease, stroke, hypertension and some of the things that might benefit prostate cancer probably reduce the risk of other diseases, as well. But if a man says, “I’m going to do this to reduce my risk of prostate cancer,” we don’t know if that’s the case.
