The results of the prostate-specific antigen (PSA) blood test, used to screen for prostate cancer, may fluctuate from year to year, according to a new study reported in the Journal of the American Medical Association (Vol. 289, No. 20: 2695–2700).

In some cases, levels that were abnormally high returned to normal on their own. This could have important implications for whether men with an elevated PSA level should get a prostate biopsy right away, according to the researchers from Memorial Sloan-Kettering Cancer Center and the National Cancer Institute.

Since the first use of the PSA blood test in the 1980s, doctors have been able to detect many more cases of prostate cancer at an earlier stage. But the test is not perfect, and several important questions have yet to be answered.

For example, it is not yet known if screening with the PSA test will save lives or prolong patients’ survival. Prostate cancer is thought to be more curable if detected at an early stage. But some doctors argue that the test may be detecting some cancers that would never cause symptoms because they are so slow growing. Treating these cancers, on the other hand, can have side effects such as impotence or incontinence.

Doctors have also had a hard time establishing an absolute “cut off” level at which more testing is needed. Most (but not all) doctors agree PSA levels below 4 ng/ml are normal, and levels over 10 ng/ml indicate that a prostate biopsy (in which tissue is removed and examined under a microscope) is needed.

But a gray zone exists for levels between 4 and 10 ng/ml. About one in four men whose PSA is in this range have prostate cancer. Some doctors recommend getting a biopsy right away. But the biopsy can be uncomfortable and carries a small risk of infection and bleeding, so other doctors suggest repeating the PSA test at a later date or using other tests, such as a free-PSA test, to get a better idea of what may be going on. Other approaches now under study include watching the trend in PSA levels over time (PSA velocity), looking at the PSA level in relation to the size of the prostate (PSA density), or deciding a course of treatment based on the patient’s age.

PSA levels are also known to be affected by certain conditions, such as inflammation of the prostate or benign prostatic hyperplasia (BPH), and by medications. Some previous studies have also suggested that levels may fluctuate over time within individuals.

In the present study, researchers examined the PSA levels of nearly 1,000 men over a four-year period. (The men, all over age 35, had the yearly blood tests done as part of another study.)

Of the 154 men who had an elevated PSA (4 ng/ml or higher) on one of the early tests, 30% returned to a normal level a year later. Similar numbers were found when the researchers used other criteria to define “abnormal” (such as using a lower cut-off level of 2.5 ng/ml or using an age-based PSA cut-off). Overall, nearly half the men who had an abnormal PSA value by any of the criteria returned to a normal level later on.

Because the PSA testing was done on samples taken a year apart, the researchers could not study how quickly the PSA levels may have changed. Still, it was clear that the levels were fluctuating over time.

“While PSA testing does lead to the early detection of prostate cancer, a single abnormal PSA level should be viewed with caution,” the authors write. “A newly elevated level should be confirmed before expensive or invasive tests, such as a prostate biopsy, are recommended.”

Because prostate cancer generally grows slowly, there would be little harm in waiting four to six weeks to repeat the test, they conclude. “Because of the apparent fluctuations in PSA levels over time, this policy would decrease the number of unnecessary biopsies, but still diagnose men within a reasonably safe time frame.”