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The use of serum prostate-specific-antigen (PSA) testing for prostate cancer has increased dramatically since it was introduced in 1986. As a result, more than 1 million additional men in the United States have been diagnosed and treated for prostate cancer. However, several studies in recent years have raised questions about the value of the screening test in actually preventing prostate cancer deaths.
“Some experts argue that routine PSA screening may be leading to overdiagnosis.
“Some experts argue that routine PSA screening may be leading to overdiagnosis.
Prostate cancer, which ranks second to lung cancer as the most common cause of death by cancer in men, is often slow-growing and may not show symptoms for 10 to 15 years. Catching it early is important because there is really no effective treatment for the disease in its advanced stages.
But some experts argue that routine PSA screening may be leading to overdiagnosis – the detection of a cancer that is not lethal. And there can be several unpleasant side effects from the treatment.
Screening guidelines have also varied:
The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial found little difference in the rate of death by prostate men who were routinely screened and those in the control group, most of whom did not receive regular screenings. After seven years, there was a 22 percent increase in the rate of prostate cancer diagnosis in the screening group as compared to the control group. Yet there was no significant reduction in mortality: 50 patients in the screening group and 44 in the control group died of prostate cancer. Results of the PLCO trial, which is ongoing, were published in the March 9, 2009, issue of the New England Journal of Medicine.
A study in the Oct. 7, 2009, Journal of the National Cancer Institute suggests that PSA screenings have led to overdiagnosis and treatment. Researchers utilized databases from the National Cancer Institute and the U.S. Census to obtain age-specific incidence of prostate cancer and patients' initial treatment following diagnosis from 1986-2005.
The increased diagnosis was most dramatic among younger men – more than tripling since 1986 in men age 50 to 59 and seven times more frequent in men under age 50.
"Given the considerable time that has passed since PSA screening began, most of this excess incidence must represent overdiagnosis," the authors wrote. "All overdiagnosed patients are needlessly exposed to the hassle factors of obtaining treatment, the financial implications of the diagnosis, and the anxieties associated with becoming a cancer patient…."
In an editorial accompanying the study, Otis W. Brawley, MD, of Emory University, warned against promoting PSA screening over the funding of projects to better understand prostate cancer.
"Many men who thought their lives were saved by being screened, diagnosed, and treated for localized prostate cancer are perplexed to learn that so few benefit," he wrote. "They may be even more amazed that this is not a new finding. What is new is the fact that many health professionals are finally accepting it as true."
At the same time, he points out the need for research into the molecular and genetic makeup of prostate cancer so that doctors can predict which localized cancers might in fact metastasize and which are likely to remain confined to the prostate.
An NCCN panel in January urged physicians to offer active surveillance to patients with prostate cancer who were at low risk of dying from their disease. Active surveillance, or "watchful waiting," involves closely monitoring these patients rather than immediately treating them, pursuing definitive treatments only if the disease appears to be progressing. Two of the major side effects of prostate surgery and radiation are impotence and incontinence.
Of the nearly 200,000 new cases of prostate cancer diagnosed in 2009, about half fall into the low-risk category according to the National Cancer Institute. A European trial conducted at the same time as the PLCO study found that PSA screening did lower the death rate; however, to prevent one death, the researchers found, 1,400 men would have to be screened and 48 treated.
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The PSA screening test is not a perfect test, but it has changed the face of prostate cancer. Twenty-five years ago, most prostate cancers were detected by doctors finding nodules during a digital rectal exam (DRE). At that stage, many of the cancers had spread beyond the prostate.
“The vast majority ofcancers we find are confined to the [prostate].”
Today, with the PSA test, the vast majority of cancers we find are confined to the organ. That has changed the mortality rate. So we have made progress using an imperfect test. That's important because we haven't found an effective therapy or vaccine for treatment of advanced stages of the disease, although research is ongoing.
The controversy over the PSA test arises from the fact that we're now finding cancers in earlier stages, some of which are non-lethal. These are low-volume, low-grade cancers that may not cause any problems. The dilemma is, however, that we can't tell you which of those cancers will cause a problem. A Scandinavian study on elderly men with low-volume prostate cancers found that 10 percent died from prostate cancer,and 8 percent died of other causes, even though their cancer had progressed. We do need to exercise better judgment in treating prostate cancer and drive research to better understand it. That's starting to happen. But we shouldn't just bury our heads in the sand and stop PSA screening.
“Our focus and our efforts should be on sorting out which prostate cancers need to be treated and which can be observed.”
PSA is a normal protein made in the prostate gland. A number of conditions can cause it to be elevated; cancer is just one of them. An enlarged prostate, infection or trauma such as from bike riding can result in higher PSA levels.
Over the years, we've used the PSA test differently. At first we relied on absolute numbers for the level of PSA, but it's hard to fit one number to everyone. More recently, we've used the PSA as an individual test, for a baseline, as in mammogram screenings. With follow-up screenings, we watch what happens to the level. If it's a flat curve, we know the individual's risk for cancer is lower. If it's a steeper curve, there is more cause for concern.
I think it's good for a man to get a baseline PSA screening beginning at age 40 if there's a family history of prostate cancer and at age 45 if not. Younger men have fewer confounding factors such as an enlarged prostate. After that, if everything is normal, they should have annual screenings. If, after 10 years, there is no increase in PSA levels, the patient can stretch out the testing intervals to two or three years. In men 73 or older who have other health issues, we should back away from routine screening.
Getting the news of a cancer diagnosis is very powerful and scary, and the depression that follows can be great. But should we react to all cancers the same way? Not all are the same. A basal cell carcinoma, for example, is certainly not as serious a skin cancer as melanoma.
The patient's response to a diagnosis of prostate cancer often depends on how the physician presents it. If I make it an emergency – "We need to get this out right away!" – of course the patient will take it that way. My job is to counsel them with current information and try to match the tumor with the appropriate treatment options. We also have to match the treatment with the patient expectations.
If we find cancer on biopsy, then we put it into a risk category, which determines the treatment. Gleason grading, which measures the volume of a tumor, is a good predictor of the behavior of the cancer. I try to educate the patient about options and he makes a choice.
At UK HealthCare, treatment options might include external radiation therapy; radical prostatectomy; or brachytherapy, with radioactive seeds placed into the prostate – all depending on the risk level. But in some cases, the option may be no treatment, particularly in a patient who is elderly or has other serious medical conditions.
It's true that some cancers are overtreated, but that doesn't mean we should stop PSA screening. Instead, our focus and our efforts should be on sorting out which prostate cancers need to be treated and which can be observed.
Dr. Strup is an urologist at UK HealthCare as well as professor of surgery and chief of urology at the UK College of Medicine.
Each issue of Advances & Insights summarizes an important piece of medical news, accompanied by commentary from a UK expert.
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