Urine-Based Biomarkers May Signal Aggressive Disease in Prostate Cancer

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(ChemotherapyAdvisor) –The urine-based biomarkers PCA3 and T2-ERG appear to signal aggressive disease in men with prostate cancer and may have future clinical utility in selecting those with low volume or low-grade disease for active surveillance, according to results of a study reported during the 2012 Genitourinary Cancers Symposium.

Increasingly, active surveillance is an alternative for managing low-risk prostate cancer; however, biomarkers are needed to distinguish men with indolent vs. aggressive disease. In a study coordinated by the Fred Hutchinson Cancer Research Center, Seattle, WA, Daniel W. Lin, MD, of the University of Washington and colleagues examined the correlation of the biomarkers PCA3 and TMRPSS2-ERG (T2-ERG) with higher volume or grade prostate cancer in an active surveillance cohort.

PCA3 is noncoding RNA found at high levels in prostate cancer relative to benign prostate cells; TMPRSS2-ERG represents the fusion of TMPRSS2, a gene regulated by androgens, with the oncogene ERG. These genetic rearrangements are found in about half of all prostate cancers and are believed to play a role in prostate cancer development, the investigators noted.

Urine was prospectively collected from 401 men following digital rectal examination as part of the multi-institutional Canary/EDRN Prostate Active Surveillance Study and PCA3 and T2-ERG levels were analyzed. Biomarker scores were correlated to clinical and pathologic variables, including tumor volume and Gleason score, and both PCA3 and T2-ERG scores were significantly associated with higher volume disease and the presence of higher grade disease.

“The ultimate goal is that men on active surveillance could use a test based on these biomarkers or others to complement biopsy and PSA data to indicate or rule out the presence of an undetected aggressive cancer or future development of aggressive cancer,” said Dr. Lin, who cautioned these initial promising results need to be confirmed in a larger study that would evaluate changes in these urine biomarkers over time, along with correlation to disease progression during active surveillance. Planned study enrollment is 1,000 men with a 5-year follow-up.

Neither PCA3 nor TMPRSS2-ERG are FDA-approved for prostate cancer detection and use in active surveillance is investigational.

The 2012 Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.


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