PSA Velocity Predicts Risk of Prostate Cancer Death

BALTIMORE, Oct. 31 -- When it comes to predicting the risks of prostate cancer, think velocity, according to researchers here.

It's the rate of change of prostate specific antigen -- not the absolute PSA level -- that is the key to telling who has a life-threatening malignancy and who doesn't, they say.

Typically, a PSA level of 4.0 ng/mL determines who needs treatment and who doesn't, noted H. Ballentine Carter, M.D., of Johns Hopkins. But PSA velocity -- the rate at which the hormone level is changing -- is a better guide and can be evaluated years before a cancer is diagnosed, Dr. Carter and colleagues reported in the Nov. 1 issue of the Journal of the National Cancer Institute.

It's known that PSA velocity is higher in men with prostate cancer and that it's associated with some surrogate markers of adverse outcomes, Dr. Carter and colleagues said. Also, a recent study has shown that a relatively high rate of change of PSA was associated with a higher risk of death after surgical intervention.

"An unanswered question is whether a higher PSA velocity could identify those men with life-threatening prostate cancer during a window of curability," the researchers said.

To answer the question, Dr. Carter and colleagues turned to the Baltimore Longitudinal Study of Aging (BLSA), which began enrolling volunteers in 1958, and compared PSA histories of 20 men who died of prostate cancer, 104 men with prostate cancer who are still alive or have died of another cause, and 856 men without prostate cancer.

The study found that PSA velocity measured 10 to 15 years before diagnosis (when most had PSA levels below 4.0 ng/mL) was associated with cancer-specific survival 25 years later. Specifically:

• Survival was 92% among men with PSA velocity of 0.35 ng/mL per year or less, but 54% among men with PSA velocity above 0.35 mg/mL per year. The finding was statistically significant at P<0.001.
• Men with PSA velocity above 0.35 ng/mL per year were more likely to die of prostate cancer than men with a lower rate. The relative risk was 4.7, with a 95% confidence interval from 1.3 to 16.5, which was significant at P=0.02

The rate of cancer deaths for men whose annual PSA velocity was above 0.35 ng/mL was 1,240 per 100,000 person-years, compared to 140 per 100,000 person-years for men with a PSA velocity below 0.35 ng/mL per year.

The implication, Dr. Carter and colleagues reported, is that "PSA velocity may help identify men with life-threatening prostate cancer during a period when their PSA levels are associated with the presence of curable disease."

In an accompanying editorial, Timothy Church, Ph.D., of the University of Minnesota School of Public Health in Minneapolis, said, "This study encourages optimism about the value of PSA velocity in predicting outcomes for prostate cancer," although the results are not definitive because of the retrospective design of the study and some deficiencies in the data.

But, Dr. Church said, two large randomized prospective trials of PSA screening are under way and they may help define the role of PSA screening in the diagnosis and treatment of prostate cancer.