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PSA -- Old Controversies, New Results
April 8, 2009
By Harvey B. Simon, M.D.
Harvard Medical School
The prostate-specific antigen (PSA) test to screen for prostate cancer is the most important issue in men's health. It is also the most controversial. That's because many experts believe prostate cancer is the exception to the rule that early detection of cancer saves lives. In fact, the PSA screening may actually do more harm than good.
Two much-anticipated studies, the results of which were released last month, were hopefully going to settle the debate over the value of the PSA. While they give us some much-needed answers, we are still a long way from settling the debate: Does PSA screening save lives by allowing doctors to treat aggressive cancers early, or does it harm men who would never die from the disease by subjecting them to the side effects of surgery, radiation, and/or hormone therapy?
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The Upside and Downside of the PSA Test
Most men in the United States over age 50 get the test, which was approved by the F.D.A. in 1994. Many men have the test repeatedly. That's no surprise, since we value the early diagnosis of cancer along with the prompt and often aggressive treatments that follow. (See Should I Have a PSA Test? for the pros and cons of testing.)
The PSA can't tell the difference between the slow growing, harmless prostate cancers and the less common, aggressive, potentially deadly tumors. In fact, the PSA can't even diagnose cancer. Instead, depending on the score, it can lead to a prostate biopsy, which is the only way to detect the cancer. If doctors see cancer cells in the tissue sample, they try to estimate how aggressive the cancer is based on its appearance.
The Big Picture
Prostate cancer is extremely common. Here's a look at the numbers:
- About 17% of American men will be diagnosed with prostate cancer during the course of their lifetimes.
- One in six American men will be diagnosed with the disease.
- The typical American man has just a 3% chance of dying from prostate cancer. In other words, only about one of every six clinically diagnosed prostate cancers will be fatal.
- Many prostate cancers never even become large enough or troublesome enough to be diagnosed clinically.
The upside of the PSA is that early diagnosis of aggressive prostate cancers can improve survival. But when screening finds cancers that would never cause symptoms or harm during the patient's lifetime, it results in the major downside of PSA screening over-diagnosis.
A cancer diagnosis usually leads to treatment, and all prostate cancer treatments carry a substantial risk of side effects. These may include sexual problems and urinary incontinence. As a result, diagnosing aggressive cancers can be lifesaving, but diagnosing harmless cancers does more damage than good.
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The American Study
The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial began in 1993. Over the next eight years, 76,693 men between the ages of 55 and 74 volunteered for the study, which took place at 10 U.S. medical centers. Scientists randomly assigned half of the men to annual PSA testing for six years, along with annual digital rectal exams (DRE) for four years. Men with PSA-test levels above 4.0 ng/ml or with abnormal DREs were advised to get further evaluation. This usually involved a prostate biopsy. Men in the comparison group continued to receive their usual medical care. Men in both groups who were diagnosed with prostate cancer were treated by their personal physicians. PLCO researchers found that both groups had similar treatments.
After seven years, the researchers found 22% more cases of prostate cancer in the men who had regular PSA screening. Even though PSA screening increased the diagnosis of prostate cancer, it did not improve survival. There were no real differences in the numbers of deaths in the two groups. About two-thirds of the men have completed another three years of follow-up in this ongoing study. The results at 10 years are similar to the previous findings.
The PLCO study will continue until all the volunteers have been evaluated for 13 years. Researchers are compiling information on treatment side effects and quality of life along with additional deaths.
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The European Study
Like the American study, the European Randomized Study of Screening for Prostate Cancer (ERSPC) began in the early 1990s. The study enrolled 162,243 men between the ages of 55 and 69. Scientists randomly assigned half of the men to receive PSA screening. The other half had their usual medical care. The study took place at medical centers in seven countries. PSA screening was performed an average of once every four years. Men with values of 3.0 ng/ml or above received prostate biopsies. Men who were diagnosed with prostate cancer were treated by their own physicians according to local guidelines.
After about 9 years of observation, 214 men in the PSA screening group and 326 men in the comparison group had died from prostate cancer. This means that screening reduced the relative risk of dying from prostate cancer by 20%. Here's what this means to you in actual numbers. The risk of dying from prostate cancer is 3 in 100 (3%) for the typical American man. A 20% reduction means that with screening, the risk drops to 2.4 in 100 (2.4% ).
This very modest benefit came at a steep price: An additional 48 men who were not at risk of dying from prostate cancer had to be treated to prevent one death from the disease.
The ERSCP scientists will continue to monitor the deaths from prostate cancer, treatment side effects and quality of life for the men.
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Should I Have a PSA Test?
Despite these major new studies, PSA testing remains a personal decision. (See Should I Have a PSA Test? for the pros and cons of testing.) But things have changed.
One Test, Several Roles
Doctors use blood PSA levels for several very different purposes.
- To diagnose prostate cancer in men who have symptoms or laboratory abnormalities that raise suspicion of the disease
- To evaluate the results of prostate cancer treatment
- To estimate the severity of benign prostatic hyperplasia (BPH), non-malignant enlargement of the gland
There is no controversy about these uses of the PSA test. The huge controversy is about the widespread use of the PSA to screen for prostate cancer in men who are free of signs and symptoms of the disease.
Before There's no evidence that PSA screening saves lives.
Now There's good evidence that screening does not save lives.
Before If a man was undecided about having a PSA test, the best recommendation is to have the test.
Now Unless a man has a particular reason to ask for the test, the best recommendation might be to skip the test.
The debate will continue, but the playing field has shifted.
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Harvey B. Simon, M.D. is an Associate Professor of Medicine at Harvard Medical School and a member of the Health Sciences Technology Faculty at Massachusetts Institute of Technology. He is the founding editor of the Harvard Men's Health Watch newsletter and author of six consumer health books, including The Harvard Medical School Guide to Men's Health (Simon and Schuster, 2002) and The No Sweat Exercise Plan, Lose Weight, Get Healthy and Live Longer (McGraw-Hill, 2006). Dr. Simon practices at the Massachusetts General Hospital; he received the London Prize for Excellence in Teaching from Harvard and MIT.