Researchers involved in the international Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial have reported that the urinary PCA3 test can predict biopsy outcome in men taking dutasteride. The details of two studies were presented at the 2010 American Society of Clinical Oncology (ASCO) Genitourinary Cancer Symposium held in San Francisco, March 5-7.
The PCA3 urinary test for prostate cancer was discovered in 1999. This test is positive in 95% of prostate cancers and negative in noncancerous tissue. According to a recent review, there have been 11 clinical studies evaluating the utility of this test to diagnose prostate cancer.[1] This urinary test measures the “number of PCA3 RNA in urine enriched with prostate cells.” The sensitivity of the PCA3 test is reported to be “less than that of serum prostate specific antigen (PSA),” but “its specificity appeared to be much better, particularly in patients with a previous negative biopsy.” Furthermore, “Recent studies have suggested that this test could be used to predict cancer prognosis.” This test is approved for use in several European countries and is marketed as Progensa®.
Dutasteride, a 5-alpha-reductase inhibitor that inhibits conversion of testosterone into dihydrotestosterone, has been found to be effective in reducing the risk of biopsy-proven prostate cancer in men with an elevated PSA with negative prostate biopsies. In the REDUCE trial, dutasteride reduced the incidence of biopsy-proven prostate cancer by 22.8%.
Researchers assessed the predictive value of the PCA3 test in patients in the placebo arm of the REDUCE trial.[2] In this study men with PSA levels of 2.5-10 had biopsies performed at two and four years of follow-up. PCA3 scores were determined in 1,072 of these patients receiving placebo. Prostate biopsies were performed at two and four years of study.
- 18% of patients subsequently had a positive biopsy for prostate cancer.
- A positive test for PCA3 was significantly predictive for a positive biopsy for prostate cancer.
- PCA3 “outperformed serum PSA.”
- A predictive model was developed incorporating serum PSA, free PSA, and PCA3 that “increased diagnostic accuracy.”
Test score at the time of a negative first biopsy predicted a positive rebiopsy two years later with a 79.1% specificity and 36.4% sensitivity. “PCA3 may be detecting undiagnosed cancers, as we found that PCA3 scores measured from biopsy negative men a year 2 of the trial predicted biopsy outcome at year 4.”
The second study presented at this symposium was carried out in men randomized to receive dutasteride.[3] This study essentially produced similar results to those in patients receiving placebo. These researchers concluded: “PCA3 can be used to predict biopsy outcome in men taking dutasteride.”
Comments: These studies suggest that the PCA3 could be a useful test added to serum PSA, especially in men with a high PSA and negative biopsies. Apparently, a clinical trial is currently underway, the results of which will be submitted to the U.S. Food and Drug Administration