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About 15 percent of older men with "normal" results on blood tests measuring prostate-specific antigen, or PSA, have prostate cancer, a recent study has found.
The study, by the government's National Cancer Institute, has created more controversy and confusion about the PSA test, widely used to screen for prostate cancer since the late 1980s. Many men get tested annually beginning at age 50, with black men and those with a family history of the disease often starting at age 45. The test, which costs about $30 to $60, is generally covered by insurance.
High PSA levels may indicate prostate cancer. Most doctors use a PSA level of 4 nanograms per milliliter of blood as the cutoff for ordering a biopsy to detect cancer. Some say the new findings mean the threshold should be lowered to a PSA of 2.5.
But increased PSA levels also can arise from enlarged prostates, common in older men. And many prostate cancers grow slowly and are unlikely to cause death. Surgery and radiation to treat prostate cancer often lead to incontinence or impotence.
Sixteen percent of men are diagnosed with the disease during their lifetimes, but only 3 percent die from it. Still, that amounts to 30,000 deaths a year --- for men, the biggest cancer killer after lung cancer.
Atlanta Journal-Constitution medical reporter David Wahlberg discussed the issue with Dr. Otis Brawley, associate director of Emory University's Winship Cancer Institute. Brawley helped design the new study when he worked at the National Cancer Institute. Q: Why has a PSA level of 4 been the cutoff for ordering a biopsy? How often do biopsies find cancer? A: In the late 1980s, a number of studies and meetings tried to figure out which PSA level picks up the most cancer. Ten was the original number, but people gravitated toward 4. Using 4 as the cutoff came about with consensus but without adequate information.
Of men who end up having cancer, a third will have an abnormal PSA but a normal digital rectal exam; a third will have a normal PSA but an abnormal rectal exam; and a third will have abnormal results on both tests. Only about 10 percent to 20 percent of men who have PSA levels above 4 have cancer. Q: Does the new study suggest that the PSA threshold for a biopsy should be lowered to 2.5? A: Some people have suggested age-adjusted cutoffs, such as 2.5 for men in their 40s or early 50s and 6 for a man in his 70s. That may be the way to go. It should be individualized and discussed between patient and physician. If a man has a family history of the disease or is very concerned about prostate cancer, this study tells us that perhaps he should not get a PSA test at all and go directly to biopsy.
If a man is in his 40s and has a PSA greater than 2.5, I am concerned he may have cancer. I would have less concern with a man in his 60s who has a PSA of 3 or 3.5. This can be an emotional decision as much as a medical decision. It is a very gray area. We need to realize that PSA tests are incredibly limited. They give us very little reassurance that a patient does not have disease --- and very little assurance that he does have disease, unless the level is very, very high. Q: Most people assume that catching prostate cancer early is beneficial, allowing doctors to treat it earlier. Is that always true? What are the potential harms of early detection? A: Some cancers do not pose harm to a patient. These are tissues that look like cancer on biopsy but grow so slowly, they are never going to harm the patient during his life span. Something else will kill him first. Studies suggest that two-thirds to three-fourths of men diagnosed through PSA tests have cancer that does not need treatment. And treatments can cause impotence, incontinence and even death. One-half of 1 percent of men who undergo surgery to remove the prostate die from the operation --- about 400 to 600 deaths a year.
We clearly cure people who do not need to be cured. I cannot tell you that we do not save lives; we probably do, but we don't know for sure. Two major studies, in Europe and in the United States, are trying to answer that question, but results won't be ready for a few years. For now, we don't have the cost-benefit ratio worked out for prostate cancer. Q: How important is the rate at which a man's PSA level increases from year to year? A: A quick rise, of 1 point or more per year, may be very indicative of prostate cancer. But the sensitivity of this is still being studied. High levels of PSA may or may not mean cancer. PSA is a protein in blood. It can increase for other reasons --- from benign enlargement of the prostate gland, from inflammation caused by sexually transmitted diseases, even from E. coli infection. Q: What other tests are being developed to screen for prostate cancer? A: There's tremendous interest in "free" vs. "total" PSA. Free PSA is floating in the blood, not bound to other proteins. If the percent of PSA that is free is low --- about 10 percent --- the man is more likely to have prostate cancer. If it is higher --- maybe 35 percent to 40 percent --- he is less likely to have cancer. We're still trying to figure out how to use this and what the cutoff point is. Some say 20 percent; others say 25 percent.
Researchers are trying to develop tests using genetic fingerprints or other proteins to determine how aggressive a tumor is, but the tests won't be ready for years. Even that wouldn't be the last step. We're going to want to do an overall health assessment, using mathematical algorithms, to figure out how to handle each patient. When it comes to prostate cancer, a guy with heart disease that will kill him in a few years is different from a guy who will live for decades. Q: Other than getting PSA tests and digital rectal exams, what can men do to prevent prostate cancer or keep it from killing them? A: No one knows for sure. Populations with diets high in soy and low in animal fat tend to have lower prostate cancer death rates. Earlier results from the new study (by the National Cancer Institute) showed that the drug finasteride --- also known as the anti-balding drug Propecia --- lowers the risk of prostate cancer by 25 percent. Some studies have suggested that vitamin E, selenium (a mineral found in many foods, especially fish and nuts) and lycopene (found in tomatoes) might have an effect, but those studies are very preliminary. We need much larger studies. For now, there is nothing anyone can do with a high degree of certainty to lower prostate cancer risk. Q: People expect medicine to have clear-cut answers. Why are prostate cancer and PSA testing so complicated? A: The more we learn, the more we learn about what we don't know. Twenty years ago, few people accepted the notion that there was a kind of prostate cancer a man could live with that didn't need to be treated. Now we know it clearly exists and is predominant. Many of us, including me, believe early detection is going to have net benefits, but we do not know that today. I believe men should be offered PSA testing, told of potential risks and benefits, and urged to make an informed choice.
Copyright 2004 The Atlanta Journal-Constitution
