Friday, May 1, 2009
For years, men have been told that the best way to deal with the threat of prostate cancer is to get regular prostate specific antigen (PSA) tests, starting for most men at the age of 50. Two recent, large, randomized studies evaluated the usefulness of this screening approach. One of the studies showed a significant, albeit modest, reduction in death from prostate cancer for previously unscreened men who received PSA testing. The other study, which included less than half as many men, showed no reduction in cancer mortality for those being screened. In addition to raising questions about the usefulness of PSA screening, these interim studies also suggest that there is a high risk of overdiagnosis and, consequently, overtreatment associated with the currently issued guidelines for prostate cancer screening.
Early-Stage Prostate Cancer: To Treat or Not to Treat?
According to the American Cancer Society, about one in every six men will be diagnosed with prostate cancer in his lifetime. With approximately 27,000 deaths from prostate cancer estimated in 2009, it is the second-leading cause of cancer death for men.
However, a significant number of men diagnosed with prostate cancer have a slow-growing version of the disease, which, if left untreated, is unlikely to cause harm. Testing for PSA levels in the blood is a highly sensitive tool used to detect the development of prostate cancer at a very early stage. It is so sensitive that it may detect even small, slow-growing cancers that do not require definitive treatment. Unfortunately, it is difficult at present to accurately distinguish between early-stage prostate tumors that will become aggressive and potentially deadly, and those that will cause no harm.
Watchful Waiting & Potential Treatment-Related Side Effects
For men with early-stage prostate cancer, doctors may recommend a process called watchful waiting (or active surveillance), in which patients are monitored closely by their doctors. If the disease becomes more active, treatment can be started. Even so, for many men a diagnosis of prostate cancer, however small and non-aggressive the tumor appears to be, presents too great a threat not to start treatment immediately.
The main treatment choices for prostate cancer, surgery and radiation therapy, may in some cases lead to significant side effects, including incontinence (the inability to control urination) and decreased sexual function. As a result, men with early-stage, non-aggressive prostate cancer may suffer needlessly from a treatment that was not required, or what is referred to as overdiagnosis.
Both of the recent PSA screening studies were published in the March 2009 issue of the New England Journal of Medicine.
Screening and Prostate Cancer Mortality in a Randomized European Study
One study [PubMed Abstract] evaluated the effect of screening with PSA testing on death rates from prostate cancer. It included 182,000 men between the ages of 50 and 74 from seven European countries. The men were randomly assigned to one of two groups. One group was offered PSA screening at an average of one test every four years. The other group, assigned as the control group, did not receive screening.
After a median nine years of follow-up, prostate cancer was diagnosed in 8.2 percent of the men in the group receiving screening, compared with 4.8 percent of the control group. In the screening group, 214 men died from prostate cancer, while 326 men in the control group died from the disease.
The study’s authors explain that while PSA screening did reduce the rate of death from prostate cancer by 20 percent, it was also associated with a high risk of overdiagnosis — and the unnecessary treatment and potential side effects that may come with it. Extrapolating from these numbers, the researchers conclude that more than 1,400 men would have to be screened and 48 additional cases of prostate cancer treated to save one life within 10 years.
Mortality Results from a Randomized Prostate Cancer Screening Trial
The second study [PubMed Abstract], running from 1993 through 2001, examined the effect of screening with PSA testing and digital rectal examination on the rate of death from prostate cancer. The study was the first report from the NCI’s Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial to consider prostate cancer mortality.
In the randomized trial, 76,693 men between the ages of 55 and 74 from ten US study centers were divided into two groups. The first group was assigned to receive annual screening, which included both PSA testing and digital rectal exam. Men in the second, control group received their usual care, which in some cases included screening, depending on their doctors’ recommendations.
After seven years of follow-up, screening was associated with a 22 percent increase in prostate cancer diagnosis. There were 2,820 prostate cancers diagnosed in the group that received screening and 2,322 cancers found in the control group, leading to 50 deaths in the screening group and 44 in the control group.
The study’s authors report that screening was associated with no significant reduction in prostate cancer mortality during the first seven to ten years of the trial. They go on to note that the risks incurred by prostate cancer treatment are substantial, and that many of these risks occur in men in whom prostate cancer would not have been detected in their lifetime had regular screening not been performed.
Screening Considerations
There are notable differences between these two large and ambitious screening studies, which can help to explain some of the differences in outcome. The most important of these is that many men in the US study (approximately 40 percent) had received PSA testing before they entered the trial, and more than half of the men continued to do so even if they were in the study’s “control” group. Based on the studies’ results, one conclusion may be that encouraging men to get PSA tests is helpful if they would not otherwise do so (as demonstrated in the European study) but not if they have already been screened and are persuaded to undergo additional PSA tests (as shown in the US study). Nonetheless, it is clear that any reduction in the number of prostate cancer deaths comes at a high cost in terms of the number of men needing to be screened, biopsied, and treated to prevent one death.
Men at high risk for developing prostate cancer — including men with a family history of the disease, African-American men (who are twice as likely as white men to develop prostate cancer), and men with certain medical conditions, such as frequent urination — should continue to receive PSA screening. The authors of the PLCO study explain that PSA screening is probably not necessary for men aged 75 and older because there has been no demonstration that it will prolong their lives. For younger men at normal risk, PSA screening is a personal decision, which each man should consider in consultation with his doctor, weighing both the potential benefits and limitations.
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