Although the new study has the strengths of being population-based and including a large number of subjects, its findings may not be generalizable to the United States, commented Judd W. Moul, MD, professor of urology and chief of the division of urologic surgery at Duke University Medical Center, Durham, N.C. As pointed out by the investigators, men in Northern Ireland in the 1990s tended to be investigated for prostate cancer only if their PSA level reached 10, a practice pattern not found in the United States.

“In my opinion, waiting until the PSA approaches 10, as was generally done in this Irish study, is waiting too long unless one is dealing with elderly or really infirm men,”

Dr. Moul told Renal & Urology News. “For most younger and healthier men less than about 60 years old, a biopsy will be indicated if the PSA stays above 2.5. For men older than about 60, many [clinicians] will ‘allow’ the PSA to go above the more traditional threshold of 4.0 before proceeding to biopsy.”

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Since the beginning of PSA testing in the United States (about 1989), the detection rate for newly diagnosed metastatic prostate cancer has declined sharply, Dr. Moul observed. At the start of the PSA era, up to 20% of men had metastases at initial presentation. Now, in the mature PSA era, this percentage has fallen to about 2% in many series. Additionally, the Surveillance Epidemiology and End Results (SEER) database shows declining population-based death rates in the United States over time since the introduction of PSA testing. “This is likely due to a combination of early detection and aggressive treatment,” Dr. Moul said.

PSA is not perfect, however. Subtle or short-term changes in PSA may not reflect cancer, but even low PSA levels (2.5-4) may be associated with prostate cancer in about 15% of men, according to data from the Prostate Cancer Prevention Trial, he said.

“From a practical standpoint, short-term changes in PSA do not generally indicate a serious situation, and follow-up PSA testing may be all that is needed rather than jumping to immediate biopsy.” The key, Dr. Moul stated, is not losing patients to follow-up.

Whether to use antibiotics to try to lower PSA—presuming prostate inflammation is suspected—is controversial, he said. “Certainly, in younger and healthier men where early detection of prostate cancer is deemed more important, the use of antibiotics may not be indicated,” he said.

For older men, however, clinicians may want to avoid opening the “Pandora’s box” of prostate cancer, so “stalling maneuvers, such as antibiotics or following PSA, becomes more appealing and acceptable,” Dr. Moul said.