A precursor of PSA detects more aggressive prostate cancer

July 11, 2003

Washington, DC - An inactive precursor form of PSA, prostate specific antigen, may prove better than the current standard of testing at detecting prostate cancer and identifying more aggressive forms of the disease, according to a study presented today at the 94th Annual Meeting of the American Association for Cancer Research (AACR).

PSA, an enzyme normally secreted by the prostate, is a well-known marker used to detect the presence of prostate cancer. As prostate cancer develops, a greater amount of PSA is released into the blood stream. Current PSA tests measure "free" and "bound" PSA, yet often fail to distinguish between slow growing cancers, which may take years to become life-threatening, and more aggressive cancers, which are likely to grow quickly and spread, requiring immediate surgery and other therapy. PSA consists of several molecular forms including proPSA, which is a precursor form of the enzyme that has been shown to be a more cancer-specific marker of prostate cancer.

"By measuring the proportion of proPSA relative to PSA, we were able to identify the men with earlier aggressive cancer who might not have otherwise been detected until it was too late to administer effective treatment," according to Stephen Mikolajczyk, staff research scientist at Beckman Coulter, Inc., San Diego. "These results may significantly alter the current standard for screening of prostate cancer by enabling detection at a cutoff below 4 nanogram(ng)/ml and reducing the number of unnecessary biopies."

The study retrospectively analyzed 1,091 blood serum specimens from men enrolled in prostate cancer screening studies who had undergone prostate biopsy (PSA 2-4 ng/ml: 320 benign, 235 cancer; PSA 4-10 ng/ml: 315 benign, 221 cancer). Throughout the 2 to 10 ng/ml range, levels of proPSA were measured using research immunoassays, developed by Mikolajczyk and his team, to determine the efficacy for detecting cancer and the ability of identifying more aggressive forms of the disease. (These assays are for research use only and are not intended for diagnostic procedures.)

Analysis of the data shows that proPSA was a better marker than the other forms of PSA - total, free, and complex - at detecting prostate cancer throughout the 2-10 ng/ml PSA range. ProPSA superiority was most pronounced in the 2-4 ng/ml range. In addition, proPSA more accurately identified aggressive forms of cancer by Gleason Score discrimination in the 2 - 4 and 4 -10 ng/ml range. The commercially available assays for free, total, and complex PSA were not effective in predicting cancer below 4ng/ml. The Gleason Score is a measure of the disruption of normal tissue architecture caused by cancer cells and is given as a scale from 1-10 after microscopic examination.

Biopsies of the prostate are usually not performed in patients with a PSA score less than 4 ng/ml. Instead, physicians often wait and conduct a follow-up exam six months to a year later. A PSA higher than 10 ng/ml indicates a high risk of cancer and the need for a biopsy to confirm the presence of the disease. For PSA results in the "grey zone" - between 4 to 10 ng/ml - a biopsy is recommended, but there is only a 30 - 40 percent chance of cancer. Since as many as 25 percent of men with PSA values below 4 ng/ml may also have prostate cancer, the cutoff mark of 4 ng/ml is controversial. Many physicians believe the cutoff should be lowered to 2 or 3 ng/ml, including study co-investigator William Catalona, MD, of Northwestern Feinberg School of Medicine, Chicago.

"As we see it now, proPSA will augment the current PSA tests by improving detection of prostate cancer, which may result in fewer cancer-related deaths in men and improved quality of life for survivors," says Mikolajczyk. ProPSA was first discovered in serum by Mikolajczyk and his team of co-workers at Beckman Coulter in 1997. Prostate cancer is the second leading cause of cancer death among men in the United States. The American Cancer Society estimates that in 2003 there will be about 220,900 new cases of prostate cancer, causing more than 28,000 deaths.
Founded in 1907, the American Association for Cancer Research (AACR) is a professional society of more than 20,000 laboratory and clinical scientists engaged in cancer research in the United States and more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals (Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention). AACR's annual meeting attracts more than 12,000 participants who share new and significant discoveries in the cancer field, and the AACR's specialty meetings throughout the year focus on all the important areas of basic, translational and clinical cancer research. Contact: Warren Froelich/AACR

Aimee Frank/Spectrum Science

In Washington, DC: (7/11-7/14)
Washington Convention Center

American Association for Cancer Research

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