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Stanford Report, February 13, 2002

Researcher challenges value of widely used prostate cancer diagnostic tool

By KENDALL MORGAN

Serendipity rather than science plays a prominent role in the current diagnosis of prostate cancer, according to Stanford University Medical Center researchers. A new study found that prostate specific antigen (PSA), a marker traditionally used by doctors as an indicator of prostate cancer risk, is clinically unreliable.

"For any level of serum PSA there is no way you can turn to a patient and say you’ve got prostate cancer," said Thomas Stamey, MD, professor of urology and primary author of the study published in the January issue of The Journal of Urology.

The results showed that low levels of PSA are not meaningfully related to prostate cancer, but are rather caused by harmless increases in pro-state size, commonly known as benign prostatic hyperplasia.

Prostate cancer is being over-diagnosed and over-treated because of the misconception that PSA is primarily a reflection of prostate cancer, Stamey said.

Levels of PSA, a normal product of the prostate gland, have been thought to increase in men with early prostate cancer. Men ages 50 or older whose PSA levels exceed a certain cutoff are monitored and may undergo prostate biopsy as standard procedure. But biopsies cannot distinguish between cancers that should be of concern and "small cancers that will never bother a patient if they live to the age of Methuselah," Stamey said.

Prostate cancer is the most common cancer in men. The American Cancer Society estimates that 189,000 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. "Prostate cancer is incredibly ubiquitous," Stamey said. "It starts in men in their 30s and by age 90, almost all men will have some cancer in their prostate." However, the risk of dying from prostate cancer is very low, Stamey added.

In order to address the relationship between PSA and prostate cancer risk, Stamey and his colleagues examined 875 prostates that had been surgically removed from cancer patients at the medical center between December 1984 and January 1997. The researchers measured the volume of cancer in each of the prostates, as well as a number of other factors known to be important to the success of prostate surgery, such as the volume of Gleason grade-4 cancer, a potentially aggressive form of the disease. They then determined whether these cancer-related factors were associated with PSA levels measured in the patients prior to surgery.

The research team found that pre-surgery PSA was not a useful predictor of any of the measured characteristics of the cancer. They also showed that surgical cure rates in men with PSA less than 4 nanograms per millimeter and men with levels as high as 10 ng/ml were no different.

The bottom line is that prostate cancer, like all other cancers, cannot be detected at an early stage by a blood test, Stamey said. "What we need is a new marker," especially one that might reflect the high-grade cancers, he said. For every 10 percent increase in these high-grade tumors, the success rate of prostate surgery declines by 10 percent. Stamey’s research lab is searching for better markers based on the genes expressed in high-grade prostate cancers.




Prostate cancer detection standards adopted by World Health Organization (12/99)