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 test depends on accurate
readings of prostate specific antigen, a
protein 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, the researchers note, is 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, said Alan Partin, 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, 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, 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
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," Partin said.
Freedland says that a variety of 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, we need to think about the
actual total amount of a biological marker rather than
concentration," he said.
This study was supported by the Department of Veterans
Affairs, Duke University Department
of Surgery and Division of Urology, Department of Defense
Prostate Cancer Research Program,
American Urological Association Foundation/Astellas Rising Star
in Urology Award, three National
Institutes of Health grants, Georgia Cancer Coalition and
American Cancer Society.