PSA Testing: Rate of Change is Better than a Magic Number

H. Ballentine Carter


Urologist H. Ballentine Carter, M.D., is startled by the results of his own research. Carter and Patrick C. Walsh, M.D., together with investigators at the Baltimore Longitudinal Study of Aging (BLSA), pioneered the idea of PSA velocity — the rate at which PSA increases over time — as a way of predicting whether a man has prostate cancer.

For as long as PSA has been in widespread use as an early detection tool for prostate cancer, Carter, The Peter Jay Sharp Foundation Scholar, has worried about the numbers. Nearly two decades ago, he cautioned (and we reported it, in Prostate Cancer Update, the predecessor of Discovery) that there were risks to locking into specific cutoff numbers. Back then, the general belief was that a prostate biopsy should be performed if a man’s PSA reached the “magic number” of 4 ng/ml.

But there is no such complacency anymore. “We now know that there is virtually no PSA below which a man can be reassured that a lethal prostate cancer does not exist,” Carter says. “Now, the problem of where to set the bar for biopsy is that there should not be one absolute bar.” Instead, Carter believes, “it makes much more sense to pay attention to what changes in PSA are telling us about the presence of a harmful prostate cancer.”

Carter and Walsh, working with colleagues at the BLSA, discovered PSA velocity in 1992. They found that in men with PSA levels between 4 and 10, a PSA velocity above 0.75ng/ml per year was a more accurate predictor of prostate cancer than any absolute level of PSA. Recently, recognizing that about 5 percent of men with PSA levels considered low — between 2 and 3 — have aggressive and potentially lethal cancers, Carter worked with colleagues at the BLSA in hopes of finding more definitive information.

The BLSA is one of the largest studies of aging in the world. Since 1958, scientists have collected and stored blood samples, at twoyear- intervals, of approximately 1,500 men. Using these stored blood samples, scientists have measured PSA over decades in men who did and did not develop prostate cancer, and in men who had aggressive and mild cancer. Together with investigators at the BLSA and at the Brady, Carter used PSA velocity to help determine the probability of dying of prostate cancer over three decades. “We found that when PSA levels were below 4 — about 10 to 15 years before men were diagnosed with their prostate cancer — a PSA velocity above 0.35 ng/ml per year was associated with a five-times greater risk of prostate cancer death when compared to a PSA velocity of less than 0.35ng/ml per year.” For example, over a 30-year period, about half of the men with a yearly PSA velocity above 0.35ng/ml died of prostate cancer, compared to only 8 percent of men with a yearly PSA velocity lower than 0.35ng/ml. “I am not aware of another test that can predict the likelihood of prostate cancer death with this accuracy prior to the diagnosis of the disease,” says Carter. He cautions that for the most accurate results using PSA velocity, the interval between tests should be at least six months, and testing should span a period of at least 18 months.

Given this discovery, Carter recommends that all men — whether or not they have a family history of prostate cancer, or are at increased risk of developing the disease — should have a baseline PSA test at age 40 — 10 years earlier than many doctors recommend. Then, depending on their baseline level, men should be tested again several times in their forties. “These early PSA tests can be used later, when a man reaches his fifties and sixties, to determine PSA velocity and the likelihood that a lethal prostate cancer is present,” he says.

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