MILAN, Italy — A
combination of 2 urine-based genetic biomarkers predicts prostate cancer better
than either biomarker alone and better than the standard serum
prostate-specific antigen (PSA), according to a new study.
The 2 markers, PCA3 and the TMPRSS2:ERG gene fusion "can help stratify men for risk
of cancer, significant cancer, and high-grade cancer at biopsy," said Jack
Groskopf, PhD, director of oncology research and development at Hologic
Gen-Probe in San Diego, California. The company is currently developing both
biomarkers.
"We're hoping to
show that the urine test results can help predict the probability of a positive
biopsy and the probability that the biopsy will find clinically significant
cancer that needs to be treated," Dr. Groskopf told Medscape
Medical News.
He presented the results here at the European Association of Urology 28th
Annual Congress.
Of the 638 subjects
involved in the study (mean age, 63 years), 66% were white, 27% were
Hispanic, and 6% were black. All were referred for an initial prostate biopsy
on the basis of elevated serum PSA (mean, 5.8 ng/mL), abnormal digital
rectal exam, or other clinical suspicion.
The researchers
collected first-catch urine prior to a 10- to 12-core prostate biopsy, and
99.8% of the specimens yielded sufficient ribonucleic acid for analysis.
A total of 43% of men
had a positive biopsy, 34% had significant cancer, defined as large tumor or high-grade
cancer that should be treated with surgery or radiation, and 18% had high-grade
cancer, Dr. Groskopf reported.
The researchers used the
combination PCA3 and TMPRSS2:ERG test scores to categorize the men by risk (1, low risk; 5, high
risk). They found that as the test scores increased, so did the risk for a
positive biopsy, a significant cancer, and a Gleason score above 6.
Table. Outcome According
to Biomarker Risk Group
|
Risk Group
|
Positive Biopsy (%)
|
Significant Cancer (%)
|
Gleason Score >6 (%)
|
|
1 (low)
|
14
|
5
|
2
|
|
2
|
22
|
14
|
5
|
|
3
|
33
|
24
|
11
|
|
4
|
56
|
45
|
25
|
|
5 (high)
|
84
|
80
|
44
|
The researchers also
compared the combination scores with those from either biomarker alone. They
found that the predictive accuracy of biopsy outcome was better with the
combination test than with either PCA3 or TMPRSS2:ERG alone.
They also found that the
predictive accuracy of significant and high-grade prostate cancer was better
with the combination test than with either test alone.
Table. Predictive
Accuracy of the Biomarkers
|
Prostate Cancer
|
PCA3 Score
|
TMPRSS2:ERG Score
|
Combined Score
|
P value
|
|
Any
|
0.73
|
0.69
|
0.76
|
<.001
|
|
Significant
|
0.75
|
0.69
|
0.79
|
<.001
|
|
High grade
|
0.74
|
0.65
|
0.77
|
.015
|
This information could
help clinicians determine which men should undergo biopsy, said Dr. Groskopf.
"For the 2
lowest-risk groups — roughly one third of subjects — the risk of finding
high-grade aggressive cancer at biopsy was only 2% to 5%, which is similar to
the risk of postbiopsy complications," he explained.
"There was a 95%
chance that biopsy would not find aggressive disease.... Whereas in the
highest-risk patients (group 5), the risk of finding significant cancer
was about 80%, which could provide more assurance that biopsy is
warranted," Dr. Groskopf noted.
"We're not trying
to replace biopsy or serum PSA. The goal of this research is to show that the
urine markers could be used in combination with PSA to help decide who should
be biopsied and, combined with the biopsy results, might help initial treatment
decisions after diagnosis."
Laurence Klotz, MD,
chief of urology at Sunnybrook Health Sciences Centre and professor of surgery
at the University of Toronto in Ontario, Canada, said he thinks the 95%
negative predictive value for higher-grade cancer is "very
impressive."
"We desperately
need a good biomarker for clinically significant prostate cancer. PCA3 looks promising as a marker for diagnosis, but
not as much for identifying the worst patients. For TMPRSS2, the data are more limited, but could be
promising. The key is to be able to exclude high-grade cancer. If you can do
that with 95% accuracy, you have something," he said.
Last year, the US Food
and Drug Administration approved the Hologic Gen-Probe's PCA3 assayProgensa, as reported at that time by Medscape Medical News.
Dr. Groskopf said that
the "test is now well established in terms of its ability to function with
serum PSA and other clinical information for the prediction of biopsy
outcome."
This study was funded by Hologic Gen-Probe, the company that is
developing the biomarkers. Dr. Groskopf is an employee of the company. Dr.
Klotz has disclosed no relevant financial relationships.
European Association of
Urology (EAU) 28th Annual Congress: Abstract 1045. Presented March 17, 2013.
