Map of life expectancy at birth from Global Education Project.

Wednesday, May 23, 2007

The PSA and errr, that other examination . . .

Okay, since I presumed yesterday to give advice to people about a problem I will never have to deal with myself, Roger wants to know what I have to say about the Prostate Specific Antigen test. Don't mind a bit.

Prostate cancer is a very interesting disease, from a public health point of view. It turns out that upon autopsy, something like 70 or 80% of men over seventy who died of other causes are found to have what would have been diagnosed as prostate cancer had it been biopsied, but they never had any symptoms of prostate cancer. (I don't remember the exact numbers and I don't have time to look them up, but it's not important -- it's the basic idea that matters.) So, the question is, did those men in fact have a "disease"?

There is unquestionably a real disease of prostate cancer. More than 30,000 American men die of prostate cancer every year. But 189,000 men are diagnosed with the disease each year. So the question becomes: how many of those men would ever have had symptoms had they not been treated, and how many would have died?

Answer: We don't know. We just don't know. Most prostate cancers are what they call indolent. The tumor grows slowly, it doesn't metastasize, it doesn't cause a problem, you live with it for years without knowing it, then you die of something else. But a minority of them are not: they become aggressive, they metastasize, they kill. We can recognize a more aggressive, dangerous cancer, but we can't tell which "indolent" ones are going to become agressive, or when, or why.

Okay, there are two methods of screening men for prostate cancer. The first is pretty basic: the doctor sticks his finger up your ass and feels your prostate gland. The second measures the level of protein in the blood, called Prostate Specific Antigen, which tends to be elevated when there is cancer present. The DRE alone can detect about 60% of prevalent cancers; adding the PSA to it brings it up to closer to 80%. Whether that is a good thing or not is the question. Nobody can even agree on the so-called Positive Predictive Value of these tests because nobody knows what a false positive is.

Here's the problem. Once you detect a prostate cancer, you're going to feel that you have to do something about it, but the treatment options aren't very pleasant. Prostatectomy can produce urinary incontinence and erectile dysfunction. Radiation therapy causes tissue damage and even raises the risk for other cancers. So detecting an asymptomatic prostate cancer might not actually be a benefit at all -- it may end up subjecting you to expensive, painful, dangerous and damaging treatment for something that was never a problem in the first place.

Well, does screening have a benefit in life expectancy at the population level? That is unknown. You can get the lowdown from the Agency for Healthcare Research and Quality here. I'll offer a brief excerpt:

The [U.S. Preventive Services Task Force]found one randomized controlled trial (RCT) and three case-control studies examining the effect of screening on prostate cancer mortality. The single RCT of PSA and DRE screening, which reported a benefit from screening, was hampered by a low rate of acceptance of screening in the intervention group (23 percent) and by flaws in the published analysis.11 No difference in the number of prostate cancer deaths was observed between the groups randomized to screening versus usual care using "intention to treat" analysis.3 Three case-control studies of screening DRE produced mixed results.12-14 A number of RCTs of PSA screening for prostate cancer are underway in both the United States and Europe, but they are not expected to report results for several years.

Data are also limited to determine whether and how much treatment of screening-detected cancers improves outcomes. Radical prostatectomy and radiation are the most commonly used treatments for localized prostate cancer, yet few well-conducted randomized controlled trials have been completed to determine whether these treatments reduce mortality or are more effective than "watchful waiting" (deferring treatment until symptoms or disease progression is evident) for organ-confined prostate cancer.

In other words, not only do we not know whether screening has any real benefits, we don't even know for sure if it's worthwhile to treat cancers that are detected by screening. It seems to me that if you aren't going to do anything even if you do find cancer, then why be screened? But if you are going to do something, and you don't even know whether it's likely to do more harm than good, then I personally would rather not know.

The bottom line?

The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examination (DRE).

Rating: I recommendation.
Rationale The USPSTF found good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes. Screening is associated with important harms, including frequent false-positive results and unnecessary anxiety, biopsies, and potential complications of treatment of some cancers that may never have affected a patient's health. The USPSTF concludes that evidence is insufficient to determine whether the benefits outweigh the harms for a screened population.

And yet, and yet, I would venture to say that 90% of the primary care doctors in the U.S. browbeat, bully and coerce their male patients into getting screened. Why? Because given the choice, doctors always want to "do something."

PS: Roger asked whether I personally submit to that, err, other test. I had to recently because I had symptoms that might have been prostatitis (turned out not to be), so it was diagnostic. What will I do in the future? Haven't come to that bridge yet, but I see no particular reason for me to undergo a DRE in the absence of any relevant symptoms. As always, though, individual risk factors, particularly family history, may change the calculus for some men.

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