Common test for prostate cancer comes under fire

Urology professor who once championed the procedure now calls it virtually useless

Amy Feldman

Looking at more than 1,300 prostate cancer samples taken at Stanford in the last 20 years, Thomas Stamey and his colleagues found that in each five-year period above, the percentage of time that a patient's PSA level indicated size of his cancer declined.

The most commonly used screening tool for detecting prostate cancer – the PSA test – is virtually worthless for predicting men’s risk of contracting the disease, medical school researchers have determined.

Stanford scientists studied prostate tissues collected in the 20 years since a high PSA test result became the standard for prostate removal. They concluded that as a screen, the test now indicates nothing more than the size of the prostate gland. The PSA test measures prostate specific antigen, a protein normally produced by the prostate gland.

“The PSA era is over in the United States,” said Thomas Stamey, MD, professor of urology and lead author of a study published in the October issue of the Journal of Urology, which was covered by CBS Evening News and Reuters among other outlets. “Our study raises a very serious question of whether a man should even use the PSA test for prostate cancer screening any more.”

The findings reflect a shift in Stamey’s thinking from 1987, when he published the original findings in the New England Journal of Medicine that linked increased blood PSA levels to prostate cancer. Over the years, Stamey has come to believe that the PSA test is no longer a useful predictor of the amount or severity of prostate cancer. He said elevated PSA levels actually reflect a condition called benign prostatic hyperplasia, a harmless increase in prostate size.

Stamey explained that the change in his thinking is due to the increased screening for prostate cancer. Now that screening is more commonplace in this country, many cancers are being caught earlier and are usually smaller – not generating enough PSA to be a good indicator of severity. By contrast, he said, the tumors encountered 20 years ago were generally so large that they generated PSA levels high enough to provide a reasonably good measure of cancer severity.

Prostate cancer is the most common cancer in men. Stamey cited a 1996 study in which researchers examined the prostates of healthy men who died from trauma, finding that 8 percent of those in their 20s already had prostate cancer. The American Cancer Society estimates that nearly a quarter of a million cases of prostate cancer will be diagnosed in the United States this year alone, and one in six men will be diagnosed with the disease at some point in their lives. Stamey said prostate cancer is a disease “all men get if we live long enough. All you need is an excuse to biopsy the prostate and you are going to find cancer.”

However, the risk of dying from prostate cancer is very low compared with lung cancer, which is the leading cause of cancer-related death in men, he said. “Almost every man diagnosed with lung cancer dies of lung cancer, but only 226 out of every 100,000 men over the age of 65 dies of prostate cancer,” he said, referring to National Cancer Institute statistics.

Stamey explained the basic dilemma as such: men whose PSA levels are above 2 nanograms per milliliter frequently undergo biopsy, which will almost always find cancer. These results do not necessarily mean that prostate removal or radiation treatment is required. “What we didn’t know in the early years is that benign growth of the prostate is the most common cause of a PSA level between 1 and 10 ng/ml,” he said.

To figure out the PSA test’s usefulness in surgery, Stamey and his team from the Department of Urology set out to document what was actually found following prostate removal, such as the volume and the grade of the cancer – two indications of the cancer’s severity. They then compared those findings with aspects that could be determined prior to surgery, such as how many of the cancers could be felt by rectal examination and the patient’s blood PSA level.

For the study, they used prostate tissue samples collected by professor John McNeal, MD, who has examined more than 1,300 prostates removed by different urologists at Stanford in the last 20 years. The researchers divided McNeal’s data into four five-year periods between 1983 and 2004 and looked at the characteristics of each cancer. They found that over time, there was a substantial decrease in the correlation between PSA levels and the amount of prostate cancer – from 43 percent predictive ability in the first five-year group down to 2 percent in the most recent one.

But the Stanford researchers concluded that the PSA test is quite accurate in one respect: in indicating the size of the prostate gland, meaning that it is a direct measure of benign prostatic hyperplasia. Stamey also noted that it remains useful for monitoring patients following prostate removal as an indicator of residual prostate cancer that has spread to other parts of the body.

A number of physicians question Stamey’s findings and contend that the test should continue to be used. Stamey disagrees. “Our job now is to stop removing every man’s prostate who has prostate cancer,” he said. “We originally thought we were doing the right thing, but we are now figuring out how we went wrong. Some men need prostate treatment but certainly not all of them.”

If the PSA test is no longer useful, the question remains as to the best course for detecting prostate cancer. Stamey recommends a yearly digital rectal exam for all men over 50. “If a cancer is felt in the prostate during a rectal examination, it is always a significant cancer and certainly needs treatment,” he said.

Unfortunately, he added, even large cancers often cannot be felt in rectal exams. His group is working on finding a blood marker that could indicate more aggressive forms of the cancer that can invade the body.

Other researchers who contributed to this work are Mitchell Caldwell, Rosalie Nolley, Marci Hemenez and Joshua Downs. The study was funded by donations to Stamey’s Prostate Cancer Research Fund at Stanford.