Testing for the presence of the highly specific prostate cancer gene PCA3 in urine predicts the results of repeat prostate biopsies more accurately than traditional prostate specific antigen testing, according to an article in the March issue of Urology.

"Men with elevated serum prostate-specific antigen (PSA) levels and negative prostate biopsy findings present a dilemma because of the lack of an accurate diagnostic test," said lead author Leonard S. Marks, MD, clinical associate professor of urology at UCLA and medical director of the Urological Sciences Research Foundation. "The results from this research study indicate that the PCA3 assay may be a new tool to assist clinicians in the treatment of these 'PSA dilemma' patients."

The study included 233 North American men (median age, 64 years) with serum prostate specific antigen levels of at least 2.5 ng/mL. All men had a previous negative biopsy and were scheduled for follow-up biopsy. Median serum prostate specific antigen level was 6.1 ng/mL.

Researchers collected urine after a digital rectal examination. Approximately 97 percent of the samples were "informative," meaning they contained adequate genetic material for analysis. Repeat prostate biopsies revealed prostate cancer in about 27 percent of the patients.

Researchers found that the risk of a positive repeat biopsy correlated with PCA3 score. Among the 26 men who had a PCA3 score of less than 5, only 12 percent had a positive repeat biopsy. In contrast, among the 18 men with a PCA3 score greater than 100, 50 percent had a positive repeat biopsy. For all men, the PCA3 research assay yielded an odds ratio of 3.6, meaning that men with an elevated PCA3 score were 3.6 times more likely to have a positive repeat biopsy than men with a normal PCA3 score.

In addition, researchers used a statistical method called receiver operating characteristic (ROC) curve analysis to assess the ability of the PCA3 research assay to predict the result of the follow-up prostate biopsy. For the PCA3 score, the area under the ROC curve was 0.68. In comparison, the serum PSA assay yielded an area under the curve of 0.52, "indicating little better than a 'coin toss' probability of predicting the presence of prostate cancer," according to the authors.
In the study, the PCA3 assay had a sensitivity of 58 percent and a specificity of 72 percent.

"About 1 million US men undergo a prostate biopsy annually to detect prostate cancer in only one-fourth of them," Marks said. "Furthermore, men with negative biopsy findings but elevated PSA levels still have the possibility of having prostate cancer. Many will undergo additional biopsies. The dollar cost, risk of morbidity, and emotional turmoil of repeat prostate biopsies are considerable, and a more accurate prostate cancer test would be an important clinical advance for this vexing problem. In this research study, the urinary PCA3 score was superior to serum PSA for predicting the outcome of repeat biopsies. The high specificity and informative rate suggest that the PCA3 research assay could have an important role in prostate cancer diagnosis."

Previous studies have shown that PCA3 is overexpressed relative to benign cells by 60- to 100-fold in more than 90 percent of prostate tumors, indicating that the gene may be a useful biomarker for prostate cancer. In contrast, serum prostate specific antigen may be elevated due to a number of benign conditions, resulting in "false positive" results and unnecessary biopsies. In fact, as many as three quarters of men suspected to have cancer based on serum prostate specific antigen testing actually have benign conditions such as benign prostatic hyperplasia.