The Hybritech® free PSA test, manufactured by Beckman Coulter, Inc., was used in the study. Hybritech free PSA is the only fPSA assay approved by the Food and Drug Administration (FDA) for clinical use to aid in distinguishing prostate cancer from benign prostate conditions.

The study compared fPSA results with the commonly used approaches of age-specific PSA reference ranges and PSA density calculations in men aged 50 years and older with total PSA results between 4 ng/mL and 10 ng/mL and who had negative digital rectal examinations.

"PSA is the best cancer tumor marker in all of medicine, but there is understandable pressure to improve its accuracy. This study shows that free PSA is the best available way to improve the accuracy of total PSA tests," said lead author of the study William J. Catalona, M.D., of the Division of Urologic Surgery at Washington University School of Medicine.

The PSA test is limited by its relative lack of accuracy in men whose PSA levels fall in the so-called "diagnostic gray zone" of 4 to 10 ng/mL. Three-quarters of the men in this range do not have cancer.

Prior to the development of the fPSA test, men in this group were routinely recommended for a prostate biopsy, which can be both painful and costly.

Physicians who use age-specific reference ranges as a follow-up to PSA testing will factor in a patient's age relative to his PSA value, while the PSA density method requires the physician to perform a costly ultrasound to calculate serum PSA levels divided by the prostate volume.

In contrast, because fPSA assays -- which measure the amount of unbound or "free" portion of prostate-specific antigen -- do not require an accompanying ultrasound, they are more cost-effective than PSA density tests.

In the new study, 773 men ages 50 through 75 had a palpably benign prostate, total PSA levels between 4 and 10 ng/mL, a negative digital rectal examination and a histologically-confirmed diagnosis.

With these patients, follow-up tests were conducted using the Hybritech free PSA assay, PSA density tests and age-specific reference range cutoffs to increase the accuracy of PSA testing for prostate cancer detection and for staging the severity of the disease.

While all three methods increased the accuracy of total PSA testing in distinguishing benign prostatic conditions from prostate cancer, age-specific PSA cutoffs were less sensitive than fPSA and missed 20 percent to 60 percent of all cancers in men over 60 years of age.

In addition, the fPSA ratio and PSA density tests both had a 95 percent cancer detection rate when the fPSA ratio of 25 percent and a PSA density level of 0.078 were used. The study also found both methods equally effective at predicting cancer aggressiveness.

The results of the study suggest that fPSA assays can be safely used as an alternative to PSA density tests -- which require ultrasounds -- as a less invasive, less costly option to increase the accuracy of PSA tests. Prostatic biopsy is required for actual diagnosis of prostate cancer.

"Results of this study are significant because they show that free PSA tests can improve the accuracy of PSA tests and are more sensitive than age-specific reference ranges," Dr. Catalona said. "They are as accurate as PSA density tests in the study, but less costly. Other studies have also shown that free PSA ratios can provide the bonus of telling patients and physicians how aggressive the cancer is."

The study was supported by a research grant from a subsidiary of Beckman Coulter.

Beckman Coulter, headquartered in Fullerton, Calif., is a leading provider of instrument systems and complementary products that simplify and automate processes in life science and clinical laboratories. The company's products are used throughout the world in all phases of the battle against disease, from pioneering medical research and drug discovery to diagnostic testing that aids in patient treatment.

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02-Aug-2000