The extra blood volume produced in the obese may so dilute levels of a telltale protein produced by prostates that the popular PSA test may be essentially useless for diagnosing prostate cancer in men carrying extra pounds, a new study in The Journal of the American Medical Association suggests.

The new research, combining data from more than 13,000 prostate cancer patients at The Johns Hopkins Hospital and elsewhere, could eventually affect the reliability of scores of other blood tests for cancer and other diseases in obese people, or at least alter the way those tests are analyzed, investigators say.

The predictive value of the PSA test depends on accurate readings of a protein, (P)rostate (S)pecific (A)ntigen continually pumped out by the prostate. When the prostate is enlarged - due to cancer or other disorders - the concentration of PSA in the bloodstream can increase, signaling the possible presence of a tumor. Physicians thus commonly regard increased PSA values as a first marker to diagnose prostate cancer, to be followed by other diagnostic tests such as physical exams and ultrasound.

Complicating the picture further, the researchers note, that both physical exams and imaging studies are more difficult in obese men.

Although recent studies have shown that PSA concentrations can be lower than expected in obese men with prostate cancer, the current research was designed to determine which of two dueling hypotheses explained this, notes Alan Partin, M.D., chief of the Department of Urology at Johns Hopkins’ Brady Urological Institute.

One idea was based on the possibility that obese men make less PSA because they tend to have less testosterone, the sex hormone that prompts PSA production. The other attributed the phenomenon to the increased amount of blood that obese men produce to support their size, which has the effect of thinning out the concentration of PSA.

Partin and Stephen Freedland, M.D., Partin’s former postdoctoral fellow who is now an assistant professor at Duke University, investigated both ideas by assessing how much total PSA obese and normal-weight men have.

Using records of patients treated for prostate cancer between 1988 and 2006 at The Johns Hopkins Hospital, Duke University and various Veterans Affairs hospitals, Partin, Freedland and their colleagues compiled information on PSA concentration and body mass index (BMI), a ratio of body weight to height that generally indicates whether someone is underweight, normal weight or overweight.

Using a standard calculation, the researchers used BMIs to estimate the amount of blood circulating in each patient’s body. A different calculation used this blood volume, along with PSA concentrations, to estimate the total amount of PSA each patient had.

As expected, PSA concentrations were typically lower in the obese patients than in the normal-weight ones, although the total amount of PSA was about the same in both groups of patients.

“It’s clear to us that excess blood had diluted PSA concentrations in that group,” says Partin.

Freedland says a variety of new tests currently in development for cancer and other diseases rely on the concentrations of disease markers similar to PSA circulating in the blood. “For these other tests just starting down the development pipeline,” he says, “we need to think about the actual total amount of a biological marker rather than concentration.”

This study was supported by the Department of Veterans Affairs, the Duke University Department of Surgery and Division of Urology, Department of Defense Prostate Cancer Research Program, the American Urological Association Foundation/Astellas Rising Star in Urology Award, National Institutes of Health Specialized Programs of Research Excellence Grant P50 CA58236, the Georgia Cancer Coalition, National Institutes of Health R01CA100938, National Institutes of Health Specialized Programs of Research Excellence Grant P50 CA92131-01A1 and the American Cancer Society.

Source: Johns Hopkins Medicine