Pro-PSA:
Possibly a Better Marker for Prostate Cancer

by William Catalona, MD

PSA testing has revolutionized the early diagnosis and treatment of prostate cancer.

Increasing evidence shows that PSA testing is also responsible for the decreasing prostate cancer death rates occurring in the US and other countries.

In the US alone, since 1995, prostate cancer deaths have decreased 21% in Caucasian men and 16% in African-American men.

But PSA testing is not perfect.

Some results are falsely positive and some falsely negative.

To improve the accuracy of PSA testing, researchers have followed a path similar to that for cholesterol testing, in which measuring different forms of PSA provides a more accurate estimate of whether or not a man has prostate cancer.

The latest advance involves measurement of pro-PSA, which may be the best marker currently available for distinguishing between PSA elevations due to prostate cancer from those due to benign conditions of the prostate.

Here is how it works:


"Measuring different forms of PSA improves accuracy of PSA testing."

Total PSA is increased with cancer, benign enlargement of the prostate, inflammation in the prostate (prostatitis), prostate cancer, after ejaculation, and trauma to the prostate gland, such as can occur with prolonged bicycle riding, having a catheter in the bladder, a digital rectal examination, or a urological procedure, such as cystoscopy or a prostate ultrasound examination.

In a man whose total PSA is between 2.5 and 10, the absolute PSA value provides relatively little clue as to what is causing the PSA to be elevated.

PSA exists in the blood serum in two general forms: free-floating PSA and PSA complexed to proteins.

With prostate cancer, more of the PSA is in the complexed form and less in the free form. Thus, in men whose PSA is between 4 and 10, measurement of the percentage of free or complexed PSA can provide further clues as to whether the PSA is elevated due to cancer or benign causes.

However, my recent studies and those from other researchers show that men with a PSA between 2.5 and 4 have a 25% chance of having prostate cancer and, therefore, should consider a biopsy.

Unfortunately, the percentage of free or complexed PSA does not provide much discrimination between cancer and benign conditions in the total PSA range of 2.5 to 4.

New research has discovered at least three forms of free PSA (called B-PSA, I-PSA, and pro-PSA). These first two forms are decreased in the blood of prostate cancer patients and pro-PSA is increased. Thus, pro-PSA is a purer marker of prostate cancer than free PSA.

My collaborators, Drs. Stephen Mikolajczyk and Harry Rittenhouse, at Beckman Coulter Inc. have developed highly specific research tests for pro-PSA. At the American Urological Association Meeting in Chicago in May 2003, my colleagues and I presented results based on blood samples from my PSA Study as well as those from a prostate cancer screening study of Dr. Georg Bartsch from the University of Innsbruck, Austria.

These studies showed that pro-PSA could distinguish between cancer and benign conditions in men with PSA values from 2.5-10 better than total PSA, free PSA, or complexed PSA.

Moreover, pro-PSA selectively identified the more aggressive forms of prostate cancer.

The American Urological Association awarded this presentation the Yamanouchi award for the best paper on prostate cancer presented at the meeting. Also, Dr. Mikolajczyk presented the team's results at the annual meeting of the American Association for Cancer Research.

I will use the pro-PSA test in the new Familial Prostate Cancer Screening Program that my colleagues, Drs, Misop Han, Norman Smith, and Christopher Gonzalez and I will initiate in the Robert H. Lurie Comprehensive Cancer Center of Northwestern Feinberg School of Medicine in January 2004.