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 (%)|
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|
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. ForTMPRSS2, 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 assay Progensa, 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.