Prostate cancer was found in 23% of men whose initially abnormal PSA levels fell to below 4 ng/mL.

Men whose PSA levels rise above 4 ng/mL—a commonly used threshold for prostate biopsy—but then decline to below this level can still harbor prostate cancer, and many of these cancers may be aggressive.

Investigators in Northern Ireland led by David Connolly, MD, of Belfast City Hospital, studied 7,052 men with initially raised PSA levels between January 1994 and December 31, 2003. All patients had at least three PSA tests within that period. Researchers followed the men for a diagnosis of prostate cancer or benign disease. The mean follow-up was 5.9 years. By the time the study ended, the men had had an average of six PSA tests.

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PSA values decreased in 71.2% of subjects, Dr. Connolly’s group reported in Prostate Cancer and Prostatic Diseases (2009;12:47-51). In 37.8% of subjects, PSA levels dropped to below 4. Of the men in this group who were subsequently investigated, 23% received a diagnosis of prostate cancer. Forty-two percent of these patients had aggressive cancers.

“These variations in PSA, even in men with prostate cancer, highlight the difficulty of interpreting short-term changes in PSA,” the authors observed.

Slightly more than 11% of prostate cancers diagnosed in the study would have been missed had biopsy been deferred in men whose PSA had normalized, they noted.

“If the decision to proceed to prostate biopsy is based on the risk of [prostate cancer’s] being diagnosed as opposed to whether the PSA value is above or below an arbitrary cutoff,” the investigators wrote, “repeating the PSA [test] is unlikely to change this risk. Therefore, a repeat PSA test after a short time period should not affect clinical decision-making, even if the PSA level were to decrease from the initial value.”