Rational approach to implementation of prostate cancer antigen 3 into clinical care.
BACKGROUND
Prostate cancer antigen 3 (PCA3) encodes a prostate-specific messenger ribonucleic acid (mRNA) that serves as the target for a novel urinary molecular assay for prostate cancer detection. The objective of the current study was to evaluate the ability of PCA3, added to measurements of serum prostate-specific antigen (PSA), to predict cancer detection by extended template biopsy.


METHODS
Between September 2006 and December 2007, whole urine samples were collected after attentive digital rectal examinations from 187 men before they underwent ultrasound-guided, 12-core prostate biopsy in a urology outpatient clinic. Urine PCA3/PSA mRNA ratio scores were measured within 1 month, and serum PSA was measured within 6 months prior to biopsy. Those measurements were related to cancer-positive biopsies.


RESULTS
Overall, 87 of 187 biopsies (46.5%) were positive for cancer. The sensitivity and specificity of a PCA3 score > or =35 for positive biopsy were 52.9% and 80%, respectively, and the positive and negative predictive values were 69.7% and 66.1%, respectively. By using receiver operating characteristic curve analysis, PSA alone resulted in an area under the curve (AUC) of 0.63 for prostate cancer detection; whereas a combined PSA and PCA3 score resulted in an AUC of 0.71. The likelihood of prostate cancer detection rose with increasing PCA3 score ranges (P > .0001), providing possible PCA3 score parameters for stratification into groups at low risk, moderate risk, high risk, and very high risk for a positive biopsy.


CONCLUSIONS
Adding PCA3 to serum PSA improved prostate cancer prediction. The use of PCA3 in a clinical setting may help to stratify patients according to their risk for biopsy and cancer detection, although a large-scale validation study will be needed to address assay standardization, optimal cutoff values, and appropriate patient populations.