The PSA Paradox
In the United States, aside from skin cancer, cancer of the prostate is the most common cancer in men. In 2007, roughly 219,000 American men were newly diagnosed with prostate cancer, and 27,000 died.
In 1986, the FDA (Food and Drug Administration) approved the PSA - prostate-specific antigen blood test - to screen for prostate cancer in men over age 50. Only now, 25 years later, is it clear whether having a PSA test helps or harms men.
The answer? Almost certainly more harmful than helpful in normal, healthy men. (However, if you've already been diagnosed with prostate cancer, you need the PSA to track your progress.)
You would think the PSA would be a great screening test
1. Since 1990, deaths from prostate cancer have declined by 1% a year, which many believe to be due to early detection from the PSA test.
2. Most of the urologists I know praise the PSA, use it all the time, and have no idea what all the fuss is about.
3. A dozen of my male patients had their prostate cancer removed when PSA screening led to a positive biopsy. They're convinced the PSA saved their lives. ("Cancer! The PSA found my cancer! Cancer!")
4. Prostate cancer either causes no symptoms or just slows down the urinary stream, just as in many healthy older men. So it's hard to tell it's there. By the time prostate cancer causes symptoms, it has often spread beyond the prostate. So if you could do it, early detection would be best.
Here's why the PSA is problematic
1. The PSA is insensitive. If you have an abnormally high PSA, the chance you have cancer is only 20%. Most positive findings are due to inflammation or benign enlargement. Roughly 30% of those with cancer have a normal PSA. So many tests are falsely positive or falsely negative.
2. Studies show that men who have a high PSA but a negative biopsy ("false positives") have a high degree of anxiety. They worry about cancer for the next two years.
3. No scientific study shows that PSA saves lives. But no adequate scientific study has ever been done.
4. What science there is shows that doing a PSA in men over age 75 causes more harm than good. This is because prostate cancer in men over 75 grows so slowly that the vast majority die of something else before their prostate cancer becomes a serious problem.
5. Radical prostatectomy (removing the prostate) leaves two-thirds of men impotent or incontinent, unable to control their urine. Radiation therapy, the major alternative to surgery, works as well as removing the prostate but frequently leads to impotence, incontinence, and/or bleeding from the rectum.
6. If you minutely examine the prostates of a hundred 65-year-old men who died of causes unrelated to their prostates, you'll find small areas of cancer in fully half. This means that tiny islands of prostate cancer are normal in men who will never develop clinical symptoms of cancer. So if a prostate biopsy shows cancer, what does that mean? How many men with a positive biopsy but no symptoms go on to develop actual disease? No one knows.
USPSTF statement and recommendation
The USPSTF found convincing evidence that prostate-specific antigen (PSA) screening can detect some cases of prostate cancer.
Benefits of Detection and Early Treatment
In men younger than age 75 years, the USPSTF found inadequate evidence to determine whether treatment for prostate cancer detected by screening improves health outcomes compared with treatment after clinical detection.
In men age 75 years or older, the USPSTF found adequate evidence that the incremental benefits of treatment for prostate cancer are small to none.
Harms of Detection and Early Treatment
The USPSTF found convincing evidence that treatment for prostate cancer detected by screening causes moderate to substantial harms, such as erectile dysfunction, urinary incontinence, bowel dysfunction, and death. These harms are especially important because some men with prostate cancer who are treated would never have developed symptoms related to cancer during their lifetime. There is also adequate evidence that the screening process produces at least small harms, including pain and discomfort associated with prostate biopsy and psychological effects of false-positive test results.
The USPSTF concludes that for men younger than age 75 years, the benefits of screening for prostate cancer are uncertain and the balance of benefits and harms cannot be determined.
For men 75 years or older, there is moderate certainty that the harms of screening for prostate cancer outweigh the benefits.
Most medical schools teach there is no effective screening test for prostate cancer.
Frankly, I'm not sure what to do. My bias is that prostate cancer is less common in men under age 65, but when it occurs, it's more serious and more likely to kill them. I suspect that false positive PSAs are less common in younger men, too. So I'm more inclined to order a PSA in men in their 50s and early 60s.
Men with a father or brother who had prostate cancer are at increased risk of developing the disease themselves. African-American men have twice the risk of Caucasians. One can make the case to screen men with increased risk. But no one knows.
Update 3/19/09: PSA screening is less paradoxical
Yesterday the esteemed New England Journal of Medicine published two large, long-term studies assessing whether screening for prostate cancer saves lives. One study said PSA screening provided no benefit and harmed a lot of men needlessly. The other said it helps a few people.
Here are some additional tidbits from these reports and the editorial that accompanies them:
- The first is from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, sponsored by the National Cancer Institute and carried out in ten centers in the United States. A total of 78,343 men age 55-74 were divided into two groups. Half received both PSA screening and rectal examinations regularly for several years. The other half were not screened, although a large minority did in fact have some PSA testing elsewhere. Few prostate cancers were found: 116 in the screening group and 95 in the control group. Deaths from prostate cancer were about the same: 50 in the screening group and 44 in the control group. Of those prostate cancers that did turn up, just as many were far advanced in the screening group as in the controls.
- The second is the European Randomized Study of Screening for Prostate Cancer (ERSPC), involving 162,243 men, again divided into screening and control groups. In the screening group, 16% of PSA tests were positive and led to biopsy. Biopsies revealed cancer in only 24% (i.e., the PSA was falsely positive in 76%). The death rate from prostate cancer was indeed 20% lower in those screened. But the absolute reduction in mortality was small: 1410 men would have to be screened -- and 48 men would have to undergo the rigors of treatment -- to prevent one prostate cancer death.
- Many prostate cancer deaths occur ten years or more after the diagnosis is made, but the studies issued their reports after only about eight years of follow-up. So neither study is definitive. They will continue to evaluate patient outcomes over the next few years and issue updated reports.
- The actual decline in death rates from prostate cancer is 4% a year since 1992, not the 1% per year I state above. But it appears that most of this improvement is from better treatment, not earlier diagnosis.
- Many people use the analogy of the proven benefit of breast cancer screening in arguing for PSA testing. But the analogy is wrong: mammography is much better at detecting breast cancers than PSA is for the prostate. And having a prostate biopsy or prostate cancer treatment is vastly more invasive -- with many more complications and bad outcomes -- than breast cancer biopsy or treatment.
These reports further undermine the utility of PSA screening. The newest recommendation is to reserve PSA testing for men at higher risk or for those understand the risk of overdiagnosis and overtreatment and who want it anyway.
PSA screening may be on life support
Yesterday the British Medical Journal (BMJ) published a new study comparing the PSA profiles of men who seven years later had developed prostate cancer with a matched group of men who didn't get cancer. As you can see in the figure copied from that paper, the distribution of PSA values in men who later developed cancer ("Cases") is almost identical to the PSA values in men who didn't ("Controls"). The only helpful statistic was if your PSA is less than 1.0, your chance of getting prostate cancer in the next ten years was extremely low. Read the paper if you know some statistics, and you'll see why this matters.
A second study from the Journal of the National Cancer Institute discovered that from 1986 to 2005, 1.3 million more men were diagnosed with prostate cancer than previously, and a million of them were treated. But since 1986 -- the year widespread PSA screening began -- the mortality rate from prostate cancer hasn't changed much. They conclude the majority of these men were overtreated: they had their prostates removed for no good reason. Particularly a concern is that the rate of being diagnosed with prostate cancer (prior to 1986 compared with afterwards) was 3.6 times greater in men in their 50s and 7.2 times greater in men under age 50. So the risk of overdiagnosis is particularly high in younger men.
I announced these results to my colleagues, who disagreed they mean anything. Each has a patient they're certain would have developed cancer if not for PSA screening. That's certainly true, but it's beside the point. The value of a PSA isn't whether it saves the lives of a few men, because taking out everyone's prostate would accomplish the same goal, at an enormous cost in complications and suffering. The point is does performing PSA itself actually save lives, and we have little evidence that it does.
One of my fellow physicians noted that an elevated PSA reading mostly reflects prostatic enlargement: the benign hypertrophy that almost every man gets. The value jumps up and down particularly severely if a man has prostatitis (inflammation or infection of the prostate). He thinks the only way the PSA is helpful is if one measures it every year for at least three years. The actual value of the PSA doesn't matter; it's how fast it changes. If the PSA value increases exponentially (say by 0.5 the first year, 1.0 the second, 1.5 or 2.0 the third, etc.), that is a clear sign of cancer. But he can't recall the reference to the study that shows this, and I've not seen it.
Update 10/31/09: PSA screening may find mostly harmless cancers
It might seem impossible, but almost everyone develops cancers that never make us sick. Our bodies control the tumors, which remain tiny islands of abnormal cells that never cause a problem.
If you screen healthy people for cancer, you want to be sure that your test reveals real cancers, not innocent clumps of abnormal cells that will never cause an illness. It turns out this is a real problem. Aggressive treatment of an innocent lesion puts you at risk of all kinds of treatment side effects, but without any benefit. This is particularly a concern in prostate cancer, where all available treatments can cause substantial side effects.
How can you tell the difference between a cancer screening test that turns up real problems from tests that find completely harmless abnormalities? One way is to find out if the rate of advanced cancers has dropped. If a lot of people have undergone the screening, but the illness and death rates haven't changed, chances are the screening test doesn't do much. Moreover, if the rate of "cancers" found zooms up while the illness and death rates stay the same, then a lot of people are being treated needlessly.
Let's contrast PSA screening with tests we know are helpful. Science has proven that screening for cancer of the cervix (opening of the uterus in women) and colon (large intestine) saves lives, and indeed the rate of deaths and advanced cancers in those areas has declined. But while screening for prostate cancer has greatly increased the number of cancers found, there's been no change in the rate of advanced prostate cancer. The death rate from prostate cancer has declined, but many people think that's due to better treatment of advanced cancer.
Last updated Fri, Mar 30, 2012
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