Diagnostic markers for prostate cancer advance beyond PSA

August 1, 2008

Research continues to progress in developing promising new oncologic markers for diagnosing prostate cancer. Ultimately, researchers hope to address the challenge of identifying a biomarker that can help physicians differentiate indolent from aggressive prostate cancer to avoid overtreatment of the disease.

Key Points

"There has been a shift in recent years to not just identifying men with prostate cancer, but identifying those men with aggressive disease who need treatment versus those who are candidates for watchful waiting," explained M. Scott Lucia, MD, director of the Prostate Diagnostic Laboratory, and associate professor of pathology at the University of Colorado Health Sciences Center, Denver. "The ideal biomarker would help us understand the biology of the tumor so we can better identify those patients who need aggressive therapy."

The serum PSA test is still considered the gold standard among prostate cancer diagnostic tools, but it has its limitations.

Drs. Abrahamsson and Lucia discussed promising new prostate cancer diagnostic tools and markers at the International Prostate Cancer Update held here.

New gene test

One test on the horizon that has researchers touting its potential benefits is the PCA3 urine test. This test identifies men with the PCA3DD3 gene-the most prostate cancer-specific gene described to date. The gene has been found to be overexpressed in more than 95% of prostate cancer cases (Cancer Res 1999; 59:5975-9). Additionally, its expression is restricted to the prostate, making it a potentially powerful diagnostic tool.

A Dutch multicenter study found the PCA3 test improves specificity in prostate cancer diagnosis and can prevent unnecessary prostate biopsies (Clin Cancer Res 2007; 13:939-43). It was found to be particularly useful in men with PSA levels between 3.0 and 15.0 ng/mL, an area often considered the PSA gray zone.

In this study, the first voided urine was collected after a digital rectal exam in 583 men with PSA levels in the gray zone. Each participant underwent a prostate biopsy. It was found that the sensitivity of the PCA3 test was 65% and the specificity was 66% compared to 47% for the PSA test. The negative predictive value was 80%. Overall, this study showed that the PCA3 test is superior to PSA in prostate cancer detection, regardless of stage and grade, and may prevent unnecessary prostate cancer biopsies.

"The urine test PCA3 is the most promising marker we have seen in awhile, especially in patients with slightly elevated PSA who have undergone repeat biopsies that turned out to be negative," Dr. Abrahamsson said. "In these patients, the urine test may play a role to help rule out whether we are talking about prostate cancer or benign prostatic hyperplasia."

"Preliminary data with PCA3 shows it might also hold promise for telling us something about tumor invasiveness," added Dr. Lucia. "Having this knowledge will aid in determining the best type of treatment for the disease."

The PCA3 test is approved for use in the European Union but is not FDA-approved.

Another exciting area in prostate cancer diagnostics is gene fusion. Researchers have identified recurrent gene fusions between TMPRSS2 and ERG or ETV1 in 80% to 90% of the examined prostate cancer tissue samples (Science 2005; 310:644-8). This translocation is highly specific for prostate cancer tumors.

"TMPRSS2 is a very promising marker," Dr. Abrahamsson said. "We need clinical trials with a larger cohort of patients to further validate this information."

"The future will be, hopefully, that we'll have less invasive means of detecting cancer," Dr. Lucia concluded, "and that we will be able to improve the performance of PSA tests with the use of new variants that are more specific for cancer versus non-cancer events."