SAN FRANCISCO—Researchers are making headway in the development of urine assays for prostate cancer (PCa) that are more accurate than PSA tests.

At the Genitourinary Cancers Symposium here, investigators presented study findings related to two urine assays, one based on a highly specific gene-fusion biomarker called TMPRSS2:ERG (T2:ERG) and the other based on the prostate cancer gene 3 (PCA 3).

In one study led by Scott Tomlins, MD, PhD, and Arul Chinnaiyan, MD, PhD, at the University of Michigan in Ann Arbor, the T2:ERG test accurately predicted the presence of clinically significant PCa at biopsy and radical prostatectomy (RP). Another study found that the PCA3 assay was more accurate than PSA in predicting outcomes of repeat prostate biopsies.

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T2:ERG is found in approximately 50% of prostate tumors. Its presence is associated with increased tumor cell growth, increased ability to invade and metastasize, and decreased apoptosis, according to John T. Wei, MD, MS, Professor of Urology at the University of Michigan in Ann Arbor, who presented study findings.

The researchers tested urine specimens obtained from 669 men after they underwent a digital rectal examination (DRE). The specimens yielded sufficient mRNA for T2:ERG analysis in 635 of 669 patients (94.9%). The assay had a specificity of 85% at a score above 100 and 95% at a score above 200 for predicting clinically significant prostate cancer at biopsy, he said. For these same scores, respectively, the specificities were 95% and 100% for predicting clinically significant PCa at RP. 

In 101 men undergoing prostatectomy, higher T2:ERG scores were associated with upgrading at prostatectomy (from biopsy Gleason score 6 to prostatectomy Gleason score 7), higher prostatectomy Gleason scores (above 6), and large tumor volume, but not prostate weight. 

“This T2:ERG test and others like it that have an ability to differentiate clinically significant cancers from the latent ones will move us into a new era of prostate cancer diagnostics where the goal is not merely to find cancers but 
to find potentially harmful cancers,” 
Dr. Wei told Renal & Urology News.

For the PCA3 study, Jack Groskopf, PhD, Director of Research and Development, Cancer Diagnostics, Gen-Probe, Inc., San Diego, and colleagues studied men in the placebo arm of the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial, a four-year study examining whether dutasteride reduces PCa risk.

All subjects in the trial had negative biopsy results at baseline and a serum PSA level of 2.5-10 ng/mL. Ten-core biopsies were obtained after two and four years. The researchers determined PCA3 scores on 1,140 urine specimens from men scheduled for biopsies at two and four years.

A total of 1,072 (94%) specimens had enough RNA for PCA3 analysis. Of these, 18% had biopsies that were positive for PCa. As PCA3 scores increased, so did the likelihood of positive biopsy results, said Leonard S. Marks, MD, Professor of Urology at the David Geffen School of Medicine at University of California-Los Angeles, who presented study findings. PCa was detected in 6% of men with a PCA3 score below 5 and in 57% of men with a score above 100. 

In addition, PCA3 measurements at year 2 of the study significantly predicted year 4 biopsy outcomes, and serum PSA and free PSA did not, 
Dr. Marks told attendees. A PCA3 threshold of 35—which he said offers the best combination of sensitivity and specificity—had a sensitivity and specificity of 36.4% and 79.1%, respectively.

PCA3 scores were significantly higher for men with a Gleason score of 7 or higher compared with lower scores. The median PCA3 score was 49.5 for patients with a Gleason score of 7 or above compared with 31.8 among those with a Gleason score below 7. The correlation of PCA3 scores with biopsy Gleason score provides additional evidence that PCA3 might be useful for identifying more aggressive PCa. 

Eric A. Klein, MD, Chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic, said 
he was excited by the results. “Both markers are unique and different 
from PSA because they are cancer-specific rather than simply prostate-specific,” 
said Dr. Klein, who was not involved 
in the T2:ERG or PCA3 research.

”The data suggest that both of these markers add independent predictive information to DRE and PSA in the detection of prostate cancer and may make screening more accurate, resulting in fewer unnecessary biopsies, as well as help select those patients 
who can be safely managed with 
active surveillance.” n