Fifteen out of every 100 older men with a normal PSA test actually has prostate cancer, a new study shows.

PSA - prostate-specific antigen - is a chemical marker given off by cells of the prostate gland. Suspiciously high PSA levels are often an early sign of prostate cancer. A PSA over 4 ng/mL usually means that a man will have to undergo needle biopsy of his prostate.

Men breathe a sigh of relief when their doctor tells them their PSA is normal. But some men with a low PSA do have cancer. Until now, it wasn’t clear how many, says researcher Charles A. Coltman Jr., MD, chair of the Southwest Oncology Group in San Antonio.

“Our study emphasizes that there is a range of PSA levels, from 0 to 4, across which a man can have prostate cancer,” Coltman tells WebMD. “There is not a clear cut cutoff based on PSA alone which allows you to define individuals who need to be biopsied.”

Driving home Coltman’s point is a dramatic picture. It shows a high-grade prostate cancer - from a man whose PSA level was less than 1. The picture and the study it illustrates appear in the May 27 issue of The New England Journal of Medicine.

Individualized Prostate Cancer Screening

Coltman says that men and their doctors can no longer rely on PSA levels alone when deciding whether to have a prostate biopsy.

“The situation now is that the individual man with his individual urologist will have to assess what the person feels are his risk factors,” he says. “In consultation with his doctor, the individual man must come to grips with the question of whether or not a biopsy should be done. It will become a more personalized interaction.”

Who’s at high risk? Men with the following factors have the highest risk of prostate cancer:

  * Age. A man’s risk of prostate cancer increases with age.
  * Race. “African American men have the highest incidence of prostate cancer and the highest death rate from prostate cancer of any men in the world,” Coltman says.
  * Family history. A man’s risk increases if his brother or father has had prostate cancer.

Prostate Cancer With a Normal PSA

In their study, Coltman and colleagues analyzed data from a clinical trial of nearly 10,000 men. After seven years, they had a prostate biopsy whether they had a high PSA or not.

About 3,000 of these men never had a PSA level of more than 4.0. Fifteen percent of these men turned out to have prostate cancer. And 15% of these cancers were life-threatening, high-grade tumors.

The chances of prostate cancer - and of high-grade cancer - went up as PSA levels rose. But high-grade cancers were seen in men at all PSA levels.

Should Doctors Look for Trouble?

How hard should doctors look for prostate cancers? In an editorial accompanying the Coltman team’s study, Johns Hopkins researcher H. Ballentine Carter, MD, notes that a man’s lifetime risk of prostate cancer is 16%. Yet his risk of dying from prostate cancer is only 3%.

“In the age range of 60 years to 80 years, about 30% to 40% of men have small prostate cancers,” Carter tells WebMD. “Now, this article tells us, we have the ability today to detect those.”

If doctors look harder for prostate cancers, they will find them. If they do this, a lot of men will have unnecessary surgery or radiation therapy. If they don’t, some men who might have been saved by early detection will die.

“We already know we are overdetecting the disease,” Carter says. “A lot of men who have prostate cancer are not going to have their disease harm or bother them during their lifetimes. Unless they were biopsied, they never would have known that they had prostate cancer during their life. The lower we set the PSA threshold, the more unnecessary treatments we’ll have.”

Like Coltman, Carter says a man’s risk factors for prostate cancer have to be taken into account. But he would be very careful about sending a man with a midrange PSA level to get a biopsy.

“If I met someone in their 60s at a PSA level of 2.5 or 3.0 or 3.5, I would say, ‘Look, there is a high probability you do not have prostate cancer. Let’s monitor your PSA over time and see if it changes,’” Carter explains. “There shouldn’t be any urgency to try to detect these tumors when PSA is in this range. These tumors grow very slowly. They still will be curable later when their PSA is 4.”

Carter warns that it’s a different story for men in their 40s. For them, a midrange PSA level may well mean trouble.

“These are the men we should be concerned about if they have a prostate level of 2.5 or 3,” he says.

Carter suggests that more important than a single PSA test is the speed at which PSA levels change over time. An increase of 0.5 ng/mL to 0.75 ng/mL during the course of a year is worrisome, he says. Coltman, however, says he wonders whether most men would be comfortable waiting for a year to find out whether they have cancer.

Coltman and Carter agree that better tests for prostate cancer are sorely needed. These yet-to-be-invented tests would find some marker on prostate cancer cells. It is hoped the marker would show not just that the cancer is there, but whether it is a cancer a man has to worry about.

“All of us men sit on a gland like that and we are all concerned,” Coltman says. “We are frantically engaged in attempts to understand the biology of prostate cancer. We frantically want to find markers that would not only be predictive of prostate cancer, but also would help identify those prostate cancers that are at high risk to go on and spread.”