Urine-Based Markers May Pinpoint Prostate Cancer Patients With Aggressive Disease

Initial results of a multicenter trial show that 2 biomarkers, PCA3 and T2-ERG, are found at high levels in prostate cancer compared to noncancerous prostate cells and correlate well with 2 indicators of aggressive prostate cancer, tumor volume and Gleason score. This study was conducted by researchers from the Fred Hutchinson Cancer Research Center, Stanford University, and Beth Israel Deaconess Medical Center, among others.

These markers may facilitate the development of a urine test that could supplement a prostate biopsy and prostate-specific antigen (PSA) levels to predict the degree of prostate cancer aggressiveness and decide whether a patient should receive treatment rather than an active surveillance, noninterventional approach (preferred for slow-growing, low-risk disease).

Urine-based markers may be able to predict the aggressiveness of disease

Daniel Lin, MD, associate professor and chief of urologic oncology at the University of Washington Department of Urology, presented the results of the study last Friday at the American Society of Clinical Oncology (ASCO) 2012 Genitourinary Cancers Symposium.

These results are preliminary with the study still ongoing. "Further study is necessary to establish the utility of these markers. Specifically, these markers need to be evaluated in larger studies and also correlated to apparent progression on active surveillance," explained Lin. "These markers will ideally not only predict which men are appropriate candidates for active surveillance, but also identify which men may progress or have aggressive disease on active surveillance, and thus should be treated immediately with curative therapy (surgery or radiation), rather than active surveillance."

PCA3 is a noncoding RNA that is found at high levels in prostate cancer compared to noncancerous prostate cells. T2-ERG is a fusion of the TMPRSS2 gene that is regulated by androgens and ERG, an oncogene. This fusion gene is found in approximately half of prostate cancers and is hypothesized to have a role in the development of prostate cancer. "The precise function of these biomarkers is not known, and it is unclear whether they are directly involved in progression or pathogenesis of prostate cancer," said Lin.

The odds ratio for a positive compared to a negative biopsy was 1.37 for PCA3 (P = .02) and 1.30 for T2-EGR (P = .0006).

A noninvasive urine-based test that could predict aggressive disease would be preferred compared to an invasive prostate biopsy. 

This result is part of broad surveillance study, the Canary Prostate Active Surveillance Study, an 8-institution consortium to identify biomarkers to predict and identify high-risk prostate cancer.
The biomarkers identified in this study were identified in an interim analysis of data from 401 men who chose active surveillance for their prostate cancer. This study is ongoing and projects to enroll a total of 1,000 men, following them for 5 years. "[Currently], risk stratification for low versus higher risk disease is primarily based on grade, stage, and PSA. Volume of cancer on biopsy is also used in some risk stratification. It is clear that over 90% of all newly diagnosed prostate cancer is treated, thus it is clear that too many potentially indolent cancers are receiving 'unnecessary' treatment-aka overtreatment, due to overdiagnosis," according to Lin.

If verified through a longer-term, large-scale study, a biomarker urine test would decrease unnecessary treatment, lowering cost and improving quality of life for some prostate cancer patients.