November 1, 2006. How fast the amount of PSA (prostate-specific antigen) in a man's blood increases is an accurate gauge of tumor aggression and danger, according to new research from Johns Hopkins University School of Medicine. Even when PSA levels are so low as to not warrant a biopsy, a fast rate of rise (high PSA velocity or PSAV) is a marker of aggressive disease.
Findings of this Hopkins study of PSAV, in this month's Journal of the National Cancer Institute, may add a new level of predictive accuracy to prostate cancer testing, the value of which has remained controversial under currently accepted guidelines, the investigators say.
"Our data provide a further argument for PSA testing that begins relatively early in life, when PSA levels are usually lower and prostate enlargement is not a confounding factor in diagnosis," says H. Ballentine Carter, M.D., the director of the Johns Hopkins Division of Adult Urology at the Brady Urological Institute and lead author of the study.
"We would recommend that men at around age 40, not 50, have their PSA checked to develop a baseline against which to compare future changes (velocity), since even a slight rise in PSA may indicate a potential for cancer down the road," Carter said.
An estimated 234,460 men in the United States will be diagnosed with prostate cancer this year, according to the American Cancer Society.
"The main debate over how to use PSA has centered on the choice of the level that is used to trigger a biopsy," says Carter, a professor at the Johns Hopkins University School of Medicine. "Lowering the level that triggers a biopsy leads to detection of more harmless cancers, and higher levels could miss the opportunity to detect an important cancer early. We have found that the rate at which a man's PSA rises may be more important than any absolute level for identifying men who will develop life-threatening cancer while their disease is still curable. In addition, PSA velocity could be a useful method for identifying those men with a prostate cancer that could be safely monitored - an approach termed 'active surveillance'."
PSA is a protein found in the bloodstream of men, produced by the prostate gland and found at increased levels in those with prostate cancer. In previous research, PSA velocity in the year before prostate cancer diagnosis has been shown to identify men who are likely not to be cured by surgery. However, Carter's latest findings show that PSA velocity can also identify men with life-threatening disease at a time when it is still curable.
Using serum samples dating as far back as 1958, frozen as part of an ongoing randomized health study of men, Carter and his team determined PSA velocity in 980 of those study participants (856 without prostate cancer, 104 with the disease and 20 who died from it) up until May of 2005. They found that the PSA velocity determined at a time when PSA levels would not have triggered a biopsy were predictive of death from prostate cancer 20 to 30 years later.
Those men whose PSA velocity was lower had a 92 percent chance of not dying of prostate cancer 25 years later; whereas those with a higher PSA velocity had a 54 percent chance of not dying of prostate cancer. The rates of prostate cancer death were 1,240 in 100,000 for subjects with a higher velocity compared to 140 in 100,000 for those with lower velocities.
Carter emphasizes that an important difference between the current research and previous studies is that the subjects in the current study were not selected, but rather taken at random from a large, ongoing study, thus more accurately representing the U.S. population.
His research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging.
Sources and links:
Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability
H. Ballentine Carter , Luigi Ferrucci , Anna Kettermann , Patricia Landis , E. James Wright, Jonathan I. Epstein , Bruce J. Trock , E. Jeffrey Metter
Journal of the National Cancer Institute, November 1, 2006.
David C. Miller, John T. Wei, Rodney L. Dunn, James E. Montie, Hector Pimentel, Howard M. Sandler, P. William McLaughlin and Martin G. Sanda.
Michigan Urology Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA. Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan. Division of Urology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.