Ross, Loeb, and Carter: Changes in PSA alone make an inadequate
"trigger for intervention."
In less than two decades, regular screening for prostate cancer has already saved thousands of lives; men are being diagnosed with cancer an average of five to 10 years earlier than they used to be, and the vast majority are diagnosed with curable disease. Could there possibly be a downside to such wonderful news? Actually, there could. Scientists have long known that some men who get prostate cancer get the very "best" kind — if there is such a thing — imaginable. It is slow-growing, mild-mannered, and it just kind of treads water, bobbing around for years in the prostate, never spreading, never causing a problem. These men used to be diagnosed with prostate cancer only at autopsy. They lived their whole lives and died of something else, and never even knew they had cancer. Today, some men diagnosed with very early, low-risk prostate cancer are choosing active surveillance instead of immediate treatment, hoping that their cancer, too, will be the "do-nothing" kind. This is not the same as "no treatment," and it's not passive, like the old "watchful waiting," which meant waiting to take action until symptoms developed — and which, unfortunately, often meant waiting until the cancer was not curable. Instead, active surveillance involves close monitoring, with repeated PSA tests, digital rectal examinations, and yearly prostate biopsies. If there is any sign that the disease has progressed, the men receive curative treatment — surgery or radiation therapy — right away.
In some men, the cancer
progressed, but their PSA hardly
changed at all.
In many practices, these men are followed simply by measuring their PSA levels; if the PSA begins to go up, the doctor recommends a biopsy. At Hopkins, we've believed for many years that PSA alone is not an accurate guide. For this reason, the guidelines established by H. Ballentine Carter, M.D have always included yearly biopsies — whether or not the PSA goes up. Recently, Hopkins residents Ashley Ross, M.D., Ph.D., and Stacy Loeb, M.D., asked what would have happened if we had just used changes in PSA alone to serve as the "trigger for intervention." In other words, says Carter, "do men really need to undergo the yearly biopsies?" The answer turns out to be yes.
Ross and Loeb studied 290 men from the Johns Hopkins Active Surveillance Program, which Carter, professor of urology and oncology, and Jonathan Epstein, M.D., the Reinhard Professor of Urologic Pathology, started in 1994. They found that PSA levels tended to change at a slightly higher rate, or velocity, in men with progression of disease, compared to men whose cancer did not progress. However, notes Ross, "some men with progression had very little change in their PSA over time, and some men without progression had large changes in PSA over time."
Thus, changes in PSA alone "were not reliable enough," says Carter, "when a man's life might depend on knowing if his cancer has progressed. For men on active surveillance, a yearly biopsy is important. It is the best way to identify cancer progression in time for curative treatment." For the greatest accuracy, the Hopkins investigators now recommend a 14-core biopsy (instead of a biopsy that takes only 12 samples), which includes two biopsies from the area of the prostate located the farthest from the rectum. This study was presented at the 2009 Annual Meeting of the American Urological Association.