Clinical utility of the prostate cancer gene 3 (PCA3) urine assay in Japanese men undergoing prostate biopsy

Abstract

What's known on the subject? and What does the study add?• It is known that a prostate cancer gene 3 (PCA3) urine assay is superior to serum PSA level or PSA-related indices for predicting a positive biopsy result in European and US men.• This is the first report on PCA3 in a large cohort of Japanese men. The diagnostic value of the PCA3 score in Japanese men was similar to those reported in European and US men. The study concludes that a combination of PSA density and PCA3 score may be useful for selecting patients who could avoid an unnecessary biopsy. Objective• To examine the diagnostic performance of the prostate cancer gene 3 (PCA3) score for prostate cancer in Japanese men undergoing prostate biopsy. Patients and Methods• This Japanese, multicentre study included 647 Asian men who underwent extended prostate biopsy with elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE).• Urine samples were collected after DRE.• The PCA3 score was determined using a PROGENSA PCA3 assay and correlated with biopsy outcome. Its diagnostic accuracy was compared with that of serum PSA level, prostate volume (PV), PSA density (PSAD), and free/total PSA ratio (f/t PSA). Results• A total of 633 urine samples were successfully analysed (the informative rate was 98%). Median PSA was 7.6 ng/mL. • Biopsy revealed cancer in 264 men (41.7%). The PCA3 score for men with prostate cancer was significantly higher than that for men with negative biopsies (median PCA3 score: 49 vs. 18; P < 0.001). The rate of positive biopsy was 16.0% in men with a PCA3 score of <20 and 60.6% in those with a PCA3 score of Ն50.• Using a PCA3 score threshold of 35, sensitivity and specificity were 66.5 and 71.6%, respectively. • The area under the curve of the PCA3 score was significantly higher than that of the f/t PSA in men with PSA 4-10 ng/mL (0.742 vs 0.647; P < 0.05).• In men with PSAD < 0.15 and PCA3 < 20, only three (4.2%) out of 72 men had prostate cancer.

Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer

“…A score of 35 is commonly accepted, whereas a score of 20-25 is used in some studies to increase the diagnostic sensitivity of the assay [23, 24]. Based on a PCA3-Score of 35, the assay has a sensitivity of 52-67%, a specificity of 72-80%, and a diagnostic accuracy of 70-77%, according to several estimates [25-28]. The highest (85%) diagnostic accuracy is achieved with PCA3-Score of 20, according to the most recent meta-analysis [29].…”

The PCA3 test for guiding repeat biopsy of prostate cancer and its cut-off score: a systematic review and meta-analysis

“…The results were much better than those using PSA. The best PSA cutoff value showed only 57.4% and 53.8% sensitivity and specificity, respectively 10111213232425. In an American study, the diagnostic accuracy of the score was evaluated in men undergoing an initial biopsy (277) and a repeat biopsy (280) 26.…”

“…Numerous studies have shown a high level of PCA3 during the first biopsy. The sensitivity and specificity have been reported to be as high as 82.3% and 89.0%, respectively, with small differences 891011. However, these results differed in repeated biopsies.…”

Addressing the need for repeat prostate biopsy: new technology and approaches

“…Several studies have sug gested a positive relationship between increased urinary PCA3 score and prostate cancer grade. [34][35][36] To demonstrate the utility of urinary PCA3 levels in predicting aggressive ness of prostate cancer on analysis of the biopsy sample, van Poppel et al 33 pooled data from two multi centre European prospective studies, comprising clinical data from over 1,000 men. 34 The mean and median urinary PCA3 scores were lower in men with biopsy Gleason scores <7 versus those with Gleason scores ≥7, stage T1c versus cancer stage T2ac cancer, ≤33% versus >33% positive biopsy cores, and in those with 'biopsy indolent' versus 'biopsy significant' prostate cancer by Epstein defi nition.…”

“…Therefore, measure ment of urinary PCA3 improves the decisionmaking process and reduces the use of unnecessary repeat biopsy procedures (Table 3). 11,32,33 The ability to predict cancer grade and aggressive ness is, arguably, of equal importance as avoiding the unnecessary use of biopsy procedures. Diagnostic tools that enable active prediction of these characteristics would enable urologists to separate patients with clini cally relevant prostate cancer needing definitive treatment from those with indolent disease, who might be better served with active surveillance.…”