To Test, Or Not to Test ... That is the Question!

Dr. William J. Catalona -- Chief of Urology at Washington University in St. Louis and designated by American Health magazine as one of the Best Doctors in America -- has some strong opinions about the value of PSA testing for prostate cancer and he has done a significant amount of research to back them up. He shared his opinions and insight during a recent interview with PERSPECTIVES' editor.

Editor: The controversy surrounding the effectiveness of the PSA blood test as a diagnostic tool for prostate cancer continues. Unfortunately, this debate is confusing to the lay population and perhaps even deters men from obtaining the test. Do you think that talking about the controversy simply keeps it alive?

Catalona: I really don't. The misinformation persists whether we talk about it or not. I do believe that it is important to debunk the myths by making sure that men have ready access to important research data and up-to-date information so that they can make their own informed decision about whether or not to request or take a PSA test. In the final analysis, it all comes down to whether or not a man cares about doing everything possible to protect his long-term health.

Basically, the debate can be summarized this way: opponents of PSA screening argue that since both screening and treatment may have side effects, we should not recommend screening until there is proof that there will be a benefit of doing so. Those who favor screening suggest that: 1) prostate cancer seldom causes any symptoms before it becomes incurable; 2) using both the PSA test and the rectal exam doubles the chances of finding the cancer when a cure is possible; 3) most of the cancers found in PSA screenings are the kind considered to be "medically important" and curable cancers; and 4) better outcomes are possible when treating early-stage prostate cancer than treating advanced disease.

It certainly appears obvious to me that, until there is a cure for advanced prostate cancer, the only practical strategy for reducing the number of deaths and suffering from this disease is to find and treat it early.

As with any argument, there is evidence on both sides of the issue. Unfortunately, a report on prostate cancer by the U.S. Preventive Services Task Force has assembled the "evidence" in an unbalanced way. The USPSTF's recommendation essentially says that one should not actively look for prostate cancer until it is incurable, or in other words...if you can't prove the benefits of the test, then don't do it. In my opinion, that view is characteristically conservative in the extreme. In the not-too-distant past, this organization also recommended against screening for colorectal cancer until faced with overwhelming evidence about the importance of finding and treating this cancer early.

Let's face it. There are very few things in life that are without risk. Yes, false negatives and false positives do occur and there will be some men who undergo biopsies based on a positive PSA who are cancer-free. But, foregoing a test that can make a life-or-death difference just doesn't make any sense to me. Especially when we are making dramatic strides in narrowing the margin of error.

The bottom line, as far as I am concerned, is that the American Cancer Society, the American Urological Association, and the American College of Radiology -- the groups who have the most experience in treating prostate cancer patients -- all recommend annual digital rectal exams and PSA testing for prostate cancer for men over 50.

Editor: Other opponents of the test seem to suggest that if a man finds out that he has prostate cancer, the treatment can "offer almost certain harm without evidence of benefit." Is that a valid reason to avoid the test?

Catalona: I certainly don't think so, but I suppose it depends upon a man's perspective. It is true that side effects can result from treatment for prostate cancer, but let's take a realistic look at them and make intelligent decisions based on all the facts instead of on 25 year-old studies that were inadequate in the first place.

There is a basic research bias here that should be acknowledged; epidemiologists and preventive health people are isolated in laboratories and do not come into regular contact with actual patients who are treated for prostate cancer. They tend to look at the data based on a societal rather than a human perspective, which embraces the basic philosophy that -- regardless of the complications -- it is "better to be alive than dead." The USPSTF, for example, never mentions that side effects (namely incontinence and impotence) can -- and are -- treated effectively, and completely ignore the fact that 30 percent of prostate cancer patients had waning sexual potency and up to 20 percent had some degree of urinary incontinence before treatment. They are basing opinions on old numbers that do not take into account today's better and "kinder" surgical techniques.

Editor: Perhaps this would be a good time to explain how the PSA test works and what research is doing to make it more accurate...

Catalona: PSA -- or prostate specific antigen -- is an enzyme produced by the prostate gland for one liquefy the gelatinous semen so that sperm can be mobile enough to accomplish fertilization. Given this unique reproductive function, it is logical that there should be a high concentration of PSA in semen. Essentially, there is only one door out, and that is through the semen.

The appearance of PSA in the blood, however, indicates that there is something wrong; that because of some disease factor, the PSA is leaking out and being absorbed into the blood. That disease could be BPH (benign prostatic hyperplasia), prostatitis, or it could be prostate cancer. In most men, the prostate gland begins to enlarge around age 50, and because the gland grows from the inside out, this growth can cause problems in urination if it compresses the urethra and constricts the flow of urine.

The PSA test determines if this unique prostate protein is present in a blood sample, and quantifies the amount on a number scale. If the PSA level is high, this provides absolutely useful information. First, it indicates that things are not normal; that some form of prostate disease exists. If it is caused by inflammation, antibiotics can be prescribed and a follow-up PSA test scheduled in a few weeks.

If the PSA is in the diagnostic gray zone (4 to 10 ng/ml), a relatively new, more complex lab test is recommended -- the free to total PSA tandem assay.

Editor: How does that work and where is it available?

Catalona: Remember about 10 years ago, everyone was concerned about their total cholesterol level. Then, research demonstrated that there were two components to this number -- "good" and "bad" cholesterol (LDL and HDL) -- and we found out that their relationship to each other was more important than the total number in predicting or preventing heart disease.

Now we have discovered a similar circumstance in PSA levels in blood. When small amounts of PSA gets into the bloodstream, the body recognizes it as an alien substance and releases proteins to bind or capture it to prevent it from breaking down other proteins in the body. Virtually all of the remaining measurable PSA in the blood is in the free form. This free PSA can be measured by a special laboratory assay.

What has been discovered is that, for whatever reason, the proportion of free PSA is lower with prostate cancer than with BPH. This is a significant finding so let's utilize it to fine-tune our ability to differentiate between benign disease and cancer before using the more invasive methods.

When a PSA test result falls in the diagnostic gray zone between 4 and 10, for example, we can be reasonably sure that there is something wrong. Ideally, the PSA test should then be accompanied or followed by an ultrasound exam and biopsy, but this is not a exam men want to think about -- much less undergo -- no matter what we say in its behalf. The free to total measurement might well provide an intermediate step before going to the next diagnostic level (the biopsy) and reduce or help eliminate the false positives.

The U.S. Food and Drug Administration has approved one PSA assay -- the Tandem-E PSA, Hybritech Inc. monoclonal antibody immunoassay -- in conjunction with digital rectal examination, as being safe and effective for the early detection of prostate cancer.

This method does require special laboratory equipment that can be expensive. However, it is proving to be invaluable in detecting curable prostate cancer, so it will be important to put it to the best possible use. Unfortunately, about 99 percent of the doctors don't know how important it is to use a pure monoclonal assay and virtually none of the patients do, so here are some practical guidelines. If a PSA test comes back in the gray zone, consider having a free to total PSA test before scheduling a biopsy. Use the traditional PSA test as a benchmark, to identify any increase in PSA level year to year, and to monitor the results of treatment.

Editor: Up to this point, in very general terms, men who had PSA levels of 4.0 or lower, who had no family history of prostate cancer, or who were not otherwise at high risk, were not tested further, especially if nothing suspicious as found in the DRE. Do you believe that this new free to total test change that number?

Catalona: You bet. In fact, I predict that cut-off number will be lowered to 2.5. We are in the process of conducting the nation's largest ongoing scientific study of prostate cancer. Since 1989, we have tested 30,000 men -- PSA and DRE -- every 6 months. We have found that if a man has less than 2.5 PSA, the chances are that he will be diagnosed with prostate cancer in the next 5 years are less than 1 percent.

There are, of course, exceptions to every rule. In General Schwarzkopf's case, his PSA test registered a count of only 1.8, but a biopsy confirmed cancer.

Men who are tested for the first time and have a PSA level of between 2.5 and 4 have a 13 to 15 percent chance of being diagnosed with prostate cancer in the next 5 years. The men whose first PSA test is between 4 and 10, but in whom no cancer is detected by biopsy, face a 28 percent chance of positive diagnosis within the next five years.

When a man's first PSA test comes back greater than 10, but a biopsy finds no cancer, his chances increase to 38 percent that he will be diagnosed with prostate cancer within the next 5 years.

Other research programs are confirming these statistics, so I think we will see that cut-off come down to 2.5. When a man's PSA is less than 2.5 and his DRE shows nothing suspicious, he will simply schedule an annual PSA.

For men who have a greater than 2.5 PSA result, a free to total test should be scheduled and, if that number is low, a biopsy should be performed for the definitive diagnosis. Perhaps this formula can help reduce some of the controversy about the false positives.

Editor: So, there's no question about your support of PSA screening...

Catalona: Absolutely none. I do not believe it is appropriate to sit around doing nothing while we wait for the perfect risk-free scenario. Risking the lives of hundreds of thousands of men during the next 10 to 15 years while we assemble data on the efficacy of treatment is unacceptable to me.

It is true that there is much more research to do on all aspects of prostate cancer and its treatment. There is no magic wand to make this deadly disease go away. But until a cure is found, we should do everything possible to discover the disease in its earliest stages and treat it aggressively in any man with more than a 10 year life expectancy. In my mind, men with prostate cancer should have two goals: one should be to live longer if they can, and the second should be to avoid dying of prostate cancer.

I think we're on the right track. Studies now show that about 75 percent of men over age 50 have had PSA tests. That is a remarkable number, and it seems to be paying off. As recently as 1985, fewer than 85,000 cases were diagnosed. Last year, 244,000 men learned they had the disease, and about 317,000 new cases will be diagnosed this year. The more this disease is discussed and studied, and there are more men like Gen. Schwarzkopf who are willing to discuss their experiences, perhaps even more men will be tested. Don't let the controversy stop you from scheduling a PSA test. It just might save your life.