Repeated measures of the ratio of free to total prostate specific antigen (PSA) in a man's blood can predict a diagnosis of prostate cancer up to six years earlier than current prediction methods. This discovery by researchers at the National Institute on Aging (NIA) and colleagues at the Johns Hopkins University School of Medicine is published in the December, 1996, journal, Urology.
PSA, an enzyme produced by the prostate gland, is found in high concentration in semen where it acts to liquefy the seminal fluid after ejaculation so that sperm can swim freely. Some PSA leaks into the blood stream from prostatic cells, more so when the prostate enlarges. Part of the PSA binds to alpha-1 antichymotrypsin (ACT), a protein that prevents PSA from destroying cells by deactivating enzymatic function. Free PSA (the unbound form of PSA) is active in the semen, and becomes inactive when it spills into the blood. Free and bound PSA make up total PSA in serum.
Men whose total PSA levels are high may have prostate cancer or benign prostatic hypertrophy (BPH), an enlarged prostate gland. Earlier studies have found that the rate of increase in total PSA levels over several years is one of the best indicators of whether prostate cancer is present.
Currently, most physicians test for total PSA only, which, when measured repeatedly over time, can predict prostate cancer up to four years before clinical diagnosis," says Dr. James L. Fozard, Associate Scientific Director for the Baltimore Longitudinal Study on Aging (BLSA) at the National Institute on Aging (NIA), one of the study's authors. "This study, however, shows that measuring the ratio of free to total PSA repeatedly over time may lead to a prediction of prostate cancer up to 10 years before clinical diagnosis of prostate cancer.
The NIA and Hopkins team measured free and total PSA levels on stored, frozen sera from 26 men with no history of prostate disease (control), 29 men with BPH, and 23 men with prostate cancer. All men in this study are participants in the BLSA, a longitudinal study of aging established in 1958. They return for follow-up visits every 2 years when they undergo a battery of tests including collection of blood samples. Four years before diagnosis, total PSA was significantly greater for men who developed prostate cancer (5.0ng/ml?0.9) compared to men with BPH (2.8ng/ml?0.3) and controls (0.8 ng/ml?0.1.) Free PSA levels were similar among groups at four years before diagnosis. However, the ratio of free to total PSA continuously decreased among cancer cases over the decade before prostate cancer diagnosis. At a time when total and free PSA levels were similar among groups (8 years before diagnosis), the ratio of free to total PSA was significantly lower for cancer cases (0.13?0.01) compared to BPH (0.17?0.01) and control cases (0.21?0.02). The values that most accurately detected prostate cancer were free to total PSA ratio of ?0.12 when total PSA was between 4.0 - 10.0ng/ml.
"The majority of men who have elevated PSA levels and have further diagnostic tests, such as prostate biopsies, do not have prostate cancer," says Dr. H. Ballentine Carter, a urologist at Johns Hopkins School of Medicine who worked on the study. Dr. Fozard adds, "This study shows that the ratio of free to total PSA may be useful in helping the physician to perdict whether prostate cancer is or is not developing." The American Cancer Society, the American Urological Society, and the American College of Radiology recommend that men have a PSA test and digital rectal exam annually, beginning at age 50. African American men and those with a family history of prostate cancer should have the same tests beginning at age 40. In 1996, an estimated 317,100 new cases of prostate cancer were diagnosed, and prostate cancer was responsible for an estimated 41,400 deaths. Prostate cancer rates are 37 percent higher for black men than white men. Between 1980 and 1990 prostate cancer incidence rates increased 65 percent, largely due to improved detection.
A free fact sheet on prostate gland changes, "Prostate Problems," is available by calling the NIA Information Center's toll-free number, 800-222-2225.
Scientists who worked on this study include: Dr. Jay D. Pearson, Merck Research Laboratories; Drs. H. Ballentine Carter, Daniel W. Chan, and Alan W. Partin, The Johns Hopkins University School of Medicine; Drs. James L. Fozard and E. Jeffrey Metter, the National Institute on Aging; and Dr. Albert A. Luderer, Dianon Systems, Inc.
The National Institute on Aging, a component of the National Institutes of Health, conducts and supports biomedical, social, and behavioral research related to the aging process, age-associated diseases, and the special needs of older people.
Pearson, J.D., A.A. Luderer, E.J. Metter, A.W. Partin, D.W. Chan, J.L. Fozard, and H.B. Carter: Longitudinal Analysis of Serial Measurements of Free and Total PSA Among Men With and Without Prostatic Cancer. Urology. 48(6A), 4-9, December, 1996.