How can prostate cancer screening be improved? Brady epidemiologist Elizabeth Platz Sc.D., M.P.H., the Martin D. Abeloff, M.D., Scholar in Cancer Prevention and colleagues are studying a group of men you might not expect to be helpful here — men who don't have prostate cancer. "We are looking at factors that can affect blood levels of PSA other than prostate cancer," she says.

This is happening in two different studies. In one, led by urologist Martin Umbehr, M.D., a postdoctoral fellow studying with Platz, "we evaluated the extent to which inflammation in the prostate, which is very common, affects PSA levels," explains Platz. With Angelo De Marzo, she was one of the first to conduct studies linking inflammation and prostate cancer. "Although urologists have long known that prostate inflammation may cause PSA to be elevated, previous studies looked at men who underwent prostate biopsies because they had an elevated PSA. Our analysis included data from 224 men from the placebo arm of the Prostate Cancer Prevention Trial," a large investigation in which men who were not diagnosed with prostate cancer during the trial itself were asked to have a biopsy when the study ended, even if they did not appear to need one.

"We only included men who had a PSA lower than 4 ng/ml and a normal digital rectal exam, and who did not have prostate cancer found in their biopsies." Platz and colleagues found that the men with more inflammation in their biopsied tissue had higher PSA levels, "and the greater the amount of inflammation, the higher the PSA level."

Although the scientists do not know exactly how inflammation raises PSA, they think that the inflammation disrupts the PSA-producing cells in the prostate and also makes the blood vessels within the prostate more permeable, causing PSA to leak into the bloodstream. Platz and colleagues hope that information from this study will one day help reduce unnecessary biopsies, "both for men who have never been screened, and men who have been screened and biopsied, but cancer was not found."

In another study, led by biostatistician Sarah Peskoe, Platz and colleagues looked to see whether testosterone affects PSA levels in the blood. "While we know that testosterone helps signal to prostate cells to make PSA, no one had quantified the association between testosterone and PSA in the blood in a general population of men who haven't been diagnosed with prostate cancer," says Platz. In this study, the investigators looked at data from 378 men, between the ages of 40 and 85, who participated in the National Health and Nutrition Examination Survey, which ran from 2001 to 2004. "We only included men who did not have a prostate cancer diagnosis and had not had a recent biopsy, rectal examination, cystoscopy, or known prostate infection or inflammation," says Platz. The scientists found that men who had higher testosterone levels also had higher PSA levels. "We also found that the odds of having a clinically elevated PSA were greater among men with higher testosterone levels. Our findings may indicate that in prostate cancer screening, American men who have higher testosterone levels may be more likely to undergo unnecessary prostate biopsy," flagged by their higher PSA. "While we are not advocating that men should have their testosterone measured at this time, we expect that knowledge of the testosterone-PSA association may help refine tools for clinical decision-making in men who have an elevated PSA." Platz and colleagues published the results of these two studies in Prostate Cancer and Prostatic Diseases, and Prostate, respectively.