Re: End of PSA Era?
- From: Leonard Evens <len@xxxxxxxxxxxxxxxxxxxxx>
- Date: Wed, 13 Jul 2005 08:46:49 -0500
george conklin wrote:
"My one wish with prostate cancer," says Dr. Thomas Stamey, a veteran researcher at Stanford University, "is that before a doctor does anything aggressive, he would tell his patient that all men will develop the disease eventually." He pauses to let the bad news sink in. "The good news," he wants doctors to add, "is that the rate of dying from prostate cancer is infinitesimal."
This is a strange use of the term "infinitesimal". The American Cancer Society estimates that this year 232,090 cases of prostate cancer will be diagnosed, and 30,350 men will die of prostate cancer. Thus the deaths ware estimated to be about 13 percent of the diagnosed cases. However, it should be kept in mind that prostate cancer has a long time horizon, so the men who die of the disease this year were diagnosed over the course of the last 15 to 20 years. In previous years, the number of diagnosed cases may have been somewhat less because the size of the vulnerable population of older men was smaller. So the 13 percent figure underestimates the death rate to some degree. Also, of course treatment during the intervening years has played some role in reducing the death rate. So the natural untreated death rate for prostate cancer is presumably higher than 13 percent.
The term infinitesimal is a technical mathematical term which is often misused by lay people. But what it usually means is that the number being discussed is very small. People might differ about what might be considered infinitesimal, but 13 pwercent is certainly not in that category by any stretch of the imagination.
Of course, Dr. Stamey, may not be talking about the ratio of deaths to diagnosed cases of prostate cancer. He may be talking about the conjectured prevalence of microscopic evidence of prostate cancer detected in autopsy studies. This incidence increases with age, and there are various studies with different estimates ranging over a fairly wide range but some go as high as 80 percent in older men. But it is very important to distinguish the kind of cancer which might be detected on autopsy with the kind which is detected clinically using current methods. The number of men diagnosed clinically at some time in life is about 15 percent and that figure has remained relatively stable for quite a long time. Let us imagine a doctor having this conversation with a man who has been diagnosed with prostate cancer who is considering treatment. Which base number should the doctor divide by? A presumed number which includes all men or the base number for men clinically diagnosed with prostate cancer? It would seem divideing by the first number would be highly misleading and totally irrelevant.
Stamey has been in a reflective mood of late because of the growing realization, by him and others, that the screening test he helped discover is far less useful for detecting prostate cancer than many had once believed. In 1987, a team led by Stamey found that high levels of prostate-specific antigen (PSA) circulating in the blood were a strong indication of prostate tumors.
Before then, the only way to detect prostate cancer was with a painful biopsy, and this is still used to confirm the disease. But with a simple PSA test , doctors thought they could weed out men who don't need the more invasive procedure, as well as spot tumors at an earlier, more treatable stage.
The test has proven a powerful draw: about half of all men over the age of 50 get annual PSA tests. Now, Stamey hopes that men will be open to the older means of screening for prostate cancer.
"I don't think PSA adds very much," he says.
The End of the PSA Era?
These second thoughts stem from a troubling variety of evidence that suggests widespread testing is possibly causing more harm than good. Although death rates from prostate cancer are lower than they were before PSA screening, these rates have also declined in countries where this type of testing is not commonly used.
I would like to see the evidence for that. It certainly hasn't in all such countries.
If one were to randomly biopsy men, as Dr. Wael Sakr of Wayne State University did on a group who were accidentally killed on the streets of Detroit, about 8 percent of those in their 20s would have prostate cancer, with the rates steadily increasing as men age. Indeed, about 80 percent will develop the disease by the age of 70.
Some of these tumors are clearly dangerous. But most are slow moving, and many prostate cancer patients can go 20 years without any need for treatment, according to a recent study led by Dr. Peter Albertson. With widespread PSA screening picking up these relatively benign tumors, Stamey fears that the tests are leading to unnecessary treatment and worry.
Stamey and Albertsen are well none critics of PSA testing. And--suprise, suprise!---they keep coming up with studies proving their point. I've looked at Stamey's last study and I didn't find it at all convincing. Albertsen's study was more interesting, but it also suffered from serious defects, which were noted by anothher article in the same issue of the JAMA. Even though, Albertsen's study did show that at least for Gleason 7 cases, the likelihood of death from prostate cancer within 5 to 10 years was pretty high.
"I've been as guilty as anyone else," he says.
Not everyone is willing to give up on PSA screening quite yet.
"We know it's not a perfect test," says Jamie Bearse, a spokesperson for National Prostate Cancer Coalition, which advocates annual PSA screening for men 40 years and older. Bearse is hopeful that newer screening tests will prove more discerning. In the meantime, he says, the PSA test is the best early detection option men have. "They would rather know, than not know."
Normal vs. Abnormal PSA
Yet it is increasingly hard to determine even a broad risk prediction from PSA testing. Traditionally, doctors used a PSA measurement of 4 as a key cut off point: lower than 4 millimeters of PSA in the blood meant that men were considered cancer free, whereas higher or equal to 4 suggested the need for a biopsy to confirm the disease.
But looking at nearly 5,500 men who had a PSA test and then at least one biopsy, researchers found this cutoff point often missed tumors or implied that men had cancers that weren't in fact really there, according to recent results published in the Journal of the American Medical Association.
Indeed, a PSA level of 4.1 millimeters accurately predicts only 20 percent of prostate cancers and leads to false alarms about 6 percent of the time. Lowering the threshold will detect more cancers, but at the price of causing men to undergo biopsies for no reason or finding many benign tumors that only need to be monitored. A PSA cutoff of 2.1, for example, would yield false readings more than 85 percent of the time to catch only slightly more than half of all tumors.
The authors of the study, led by Dr. Ian Thompson of the University of Texas Health Science Center in San Antonio, call for a substantial "reeducation" effort on the increasingly murky role of PSA. "It will be a challenge to the medical community to change the long held notion that there is a 'normal' PSA level," the authors write.
Researchers still hold out hope for measuring PSA velocity, the rise of PSA over time that gives an indication if the tumor is growing. As an initial detection tool, Stamey says that doctors should return to looking at increasing age, along with a family history of the disease, as a way of determining who may be at greater risk for prostate cancer and in need of a biopsy to catch tumors early.
Other than that, he adds, "We have as much a way of predicting who will need a biopsy based on looking at someone's eyes." Ongoing studies are continuing to look at whether PSA testing saves lives, and the American Cancer Society and other test supporters urge men to discuss the pros and cons of screening with their doctors. But the creator of the PSA test is calling for the end.
"All men will develop a prostate cancer," says Stamey. "That's a given."
.
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