Some Men with Low PSAs Have Prostate Cancer:
Most Cancers Found Are Not Likely to Be Clinically Significant
Men with low PSA (prostate specific antigen) levels on screening
tests can still have prostate cancer, according to a study * released
today by scientists from the National Cancer Institute (NCI), part
of the National Institutes of Health, and the Southwest Oncology
Group, an NCI-funded network of researchers. In this study, prostate
cancers were detected by biopsy in men with normal PSA levels.
"The good news is that the vast majority of these cancers
were low and intermediate grade, which often are not clinically
significant," said Leslie Ford, M.D., associate director for
clinical research in NCI's Division of Cancer Prevention, who participated
in the research.
"This was the first systematic study of men with PSA levels
from 0 to 4 nanograms per milliliter (ng/ml). It shows that cancer
of the prostate can be present in men with 'normal' PSAs,"
said Ian Thompson, M.D., University of Texas Health Science Center
at San Antonio, who led the study. Doctors often use the value of
4.0 ng/ml or greater as the trigger for further investigation, such
as a prostate biopsy. A PSA level below 4.0 is generally considered
Prostate cancer clinicians often say that men are much more likely
to die with prostate cancer than from it. According to recent autopsy
studies, many men over age 50 have early, undiagnosed prostate cancer.
Clinicians concur that most early cancers remain harmless, though
some may progress to clinically significant disease.
The 2,950 men in this study were from the "control arm"
of the Prostate Cancer Prevention Trial (PCPT), an NCI-funded study
that found in 2003 that the drug finasteride reduced by 25 percent
a man's chances of getting prostate cancer.
Men in the control arm were given a placebo, or sugar pill, instead
of finasteride and, like the men on the finasteride arm, received
annual prostate screening for seven years with a PSA test and a
digital rectal exam (DRE). All men in PCPT entered the trial at
age 55 or above, had an initial PSA level of 3 ng/ml or less, and
a normal DRE. All were asked to undergo an end-of-study prostate
biopsy. The report released today focused on men at low risk of
having prostate cancer the 2,950 men on the placebo arm who
had normal DREs and PSAs less than or equal to 4 ng/ml for the seven-year
Since the late 1980s, PSA tests have been widely used in the United
States in an attempt to detect prostate cancer at an early stage.
However, PSA testing has never been proven to reduce the risk of
dying from prostate cancer. Not all prostate cancer detected by
PSA screening is clinically relevant and, therefore, screening carries
a risk of "over-diagnosing" the disease, which could lead
to unnecessary surgery or radiation therapy. Thus, PSA testing is
not a universally recommended screening procedure. An ongoing NCI
study is addressing the issue of whether PSA screening reduces the
risk of death from prostate cancer.
"The main study finding was that 15 percent of the men in
the PCPT control arm had a positive end-of study biopsy despite
having PSA levels below 4 ng/ml and normal DREs throughout the study,"
Importantly, the study also found that only 2.3 percent of men
in the PCPT control arm with PSA levels of 4 ng/ml or less had high-grade
cancers. For men with a PSA of 2 or lower, the chance of having
a high-grade cancer was even lower 1.4 percent. Grade was
measured by Gleason score, a system that ranks tumors from 2 to
10 based on their appearance under the microscope. High-grade tumors
Gleason scores of 7 to 10 often grow more quickly
and may be more likely to spread than lower-grade tumors.
Gleason scores of the highest grades 8 or 9 were
found in only seven participants, or 0.2 percent of men in the PCPT
control arm. Most of the men with prostate cancer, 349 of them (78
percent), had Gleason scores of 5 or 6.
"Most of these men would not have been diagnosed if they had
not taken part in this study, since biopsies are not routinely performed
in men with such low PSA levels," said Ford.
"We need better methods to distinguish the harmless, slow-growing
cancers from the more aggressive ones," continued Ford. "If
more biopsies are performed at lower PSA levels, more cancers will
be found and treated. But some men would undergo treatment, and
the risks associated with it, for tumors that would never have been
Treatment for prostate cancer can sometimes lead to impotence,
urinary incontinence, and other problems, causing a substantial
health burden for men.
"Lowering the PSA threshold for proceeding to prostate biopsy
would increase the risks of overdiagnosing and overtreating clinically
unimportant disease," said Thompson.
NCI-funded researchers are looking for ways to determine which
men harbor aggressive tumors. The NCI Early Detection Research Network
(EDRN) has a Prostate Collaborative Group, which is applying a variety
of strategies to find ways to detect prostate cancer early. Some
scientists are using the new tools of genomics and proteomics to
look at how gene expression patterns and proteins in the blood may
differ in men with aggressive tumors vs. those with slow-growing
"There is a great need for methods, beyond tumor grade, to
better predict which men have prostate cancers requiring treatment,"
Prostate cancer is the most common cancer in men, after skin cancer.
It is estimated that approximately 230,110 men in the United States
will be diagnosed with the disease this year, and about 30,000 men
will die from it.
For information about cancer, please visit the NCI home page at
http://cancer.gov or call the NCI's Cancer Information Service at
* Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes
HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman
CA. Prevalence of Prostate Cancer among Men with a Prostate-Specific
Antigen Level = 4.0 ng per Milliliter. New England Journal of Medicine,
May 27, 2004; 350(22):2239-2246