New, non-invasive prostate
cancer test beats PSA in detecting prostate cancer, researchers report
Simple urine test leads to more accurate diagnoses, fewer false-positive results
PHILADELPHIA
– An experimental biomarker test developed by researchers at the
University of Michigan more accurately detects prostate cancer than any
other screening method currently in use, according to a study published in
the February 1 issue of Cancer Research, a journal of the American
Association for Cancer Research.
The
researchers say a simple urine test that screens for the presence of
four different RNA molecules accurately identified 80 percent of patients
in a study who were later found to have prostate cancer, and was 61
percent effective in ruling out disease in other study participants.
This
is far more accurate than the PSA blood test currently in use worldwide,
which can accurately detect prostate cancer in men with the disease but
which also identifies many men with enlarged prostate glands who do not
develop cancer, researchers say. Even the newer PCA3 test, which screens
for a molecule specific to prostate cancer and which is now in use both in
the U.S. and Europe is less precise, they say.
“Relative
to what is out there, this is the best test so far,” said the study’s
lead author, Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center
for Translational Pathology at the University of Michigan.
He
also says that this “first generation multiplex” biomarker test will
likely be improved upon as researchers continue to uncover the molecular
underpinnings of prostate cancer.
“We
want to develop a test to allow physicians to predict whether their
patients have prostate cancer that is so accurate a biopsy won’t be
needed to rule cancer out,” Chinnaiyan said. “No test can do that
now.”
Chinnaiyan
and the Michigan researchers developed the test based on their recent
finding that gene fusions – pieces of chromosomes that trade places with
each other, causing two genes to stick together - are common in prostate
cancer, and that by overriding molecular switches that turn off excess
growth, they may be the causative factor in some forms of the disease. In
2005 they identified a prostate-specific gene called TMPRSS2 which fuses
with either ERG or ETV1, two genes known to be involved in several types
of cancer. In 2007, they identified another five genes that fuse on to ERG
or ETV1 to cause prostate cancer.
In the current study, researchers built upon the PCA3 test by screening
for six additional biomarkers, including TMPRSS2:ERG as well as some
molecules generally over-expressed in prostate cancer, and some which are
over-expressed in specific cancer subtypes.
Researchers
collected urine samples from 234 men with rising PSA levels before they
underwent prostate biopsy at a University of Michigan urology clinic.
Among this group, biopsy results confirmed a diagnosis of prostate cancer
in 138 patients; 96 patients were cancer-free.
Correlating
the urine biomarker test results with the biopsy data, researchers found
that, in combination, four of the seven biomarkers were significant
predictors of prostate cancer: GOLPH2, which is generally over-expressed
in prostate cancer; SPINK1, over-expressed in a subset of these cancers;
the PCA3 transcript expression; and TMPRSS2:ERG fusion status. Of the
seven markers, only PCA3 had been previously reported as a diagnostic
biomarker.
When
tested as individual biomarkers, GOLPH2, PCA3, and SPINK1 each
outperformed PSA, which had identified all of the men in the study as
potentially positive for prostate cancer. “PSA was not predictive at
all,” Chinnaiyan said. “You might as well have flipped a coin.”
The
combination of the four biomarkers achieved a specificity and positive
predictive value of greater than 75 percent, which they found to be five
percent better than use of a PCA3 test alone, he says. Specificity is the
probability that a test indicates a negative result if a person does not
have a disease, and the positive predictive value is the proportion of
patients with positive test results who are correctly diagnosed.
Chinnaiyan
believes that any tests that are developed and widely tested would first
be used to supplement a PSA blood screen.
The
study was funded by the Early Detection Research Network, Department of
Defense, the National Institutes of Health, the Prostate Cancer
Foundation, and Gen-Probe Incorporated of San Diego. The gene fusion
technology has been patented by the University of Michigan and licensed to
Gen-Probe Inc, which is also developing the PCA3 screening test.
Chinnaiyan is a paid consultant to Gen-Probe.
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