PCA3 Materials & News

Aubin SMJ, Reid J, Sarno MJ, Blase A, Aussie J, Rittenhouse H, Rittmaster R, Andriole GL, Groskopf J. J Urol 2010;184:1947-52

• This analysis of the large multicentre REDUCE (REduction by DUtasteride of prostate Cancer Events)  trial, including men with a prostate specific antigen (PSA) 2.5-10 ng/mL and a prior negative biopsy, validated the PCA3 test in the largest repeat biopsy cohort to date including 1,140 placebo-treated men. Increased PCA3 Scores were associated with an increased risk of a current positive repeat biopsy and were also predictive of future biopsy outcomes. PCA3 scores were indicative of biopsy Gleason score. Combining PCA3 with PSA and other prostate cancer (PCa) risk factors significantly increased the diagnostic accuracy
• The REDUCE trial was an international, double-blind, 4-year, randomised, placebo-controlled trial evaluating the effect of dutasteride on the risk of PCa in men with a PSA level of 2.5-10 ng/mL and a negative baseline biopsy. At baseline, 2 and 4 years, 10-core biopsies were performed. PCA3 Scores were determined for 1,140 placebo-treated men before the year 2 and/or the year 4 biopsy
• The informative rate was 94% (informative rate: % of urine samples providing sufficient mRNA for PCA3 analysis)
• PCa was detected in 17.7% of subjects during 4-year follow-up, with the majority being Gleason score 6 (69.5%) and 7 (28.9%) tumours
• In contrast to PSA, PCA3 was independent of the prostate volume
• An increasing PCA3 Score correlated with an increasing probability of a positive repeat biopsy. Median PCA3 Scores in men with a negative repeat biopsy were 15.3 and 16.9 at year 2 and 4, respectively. Median PCA3 Scores were statistically significantly higher at year 2 (P=0.0013) and year 4 (P=0.0050) if PCa was diagnosed at year 4 The median PCA3 Score was statistically significantly higher in men with a positive repeat biopsy (33.8) vs. those with a negative biopsy during the study (16.7; P<0.0001; Figure)
• Univariate logistic regression analysis showed that men with a PCA3 Score > 35, had a 3.5-fold increased risk of a current positive repeat biopsy (P<0.0001)
• At a PCA3 Score cut-off of 35 the sensitivity was 48.4% and specificity 78.6%
• Receiver Operating Characteristic (ROC) curve analysis revealed a higher Area Under the ROC Curve (AUC ROC) for PCA3 (0.693) vs. serum PSA (0.612; P=0.0077) and %free PSA (0.637; P=0.0645) for predicting repeat biopsy outcome
• The median PCA3 Score was statistically significantly higher in Gleason score > 6 tumours vs. ≤ 6 tumours (49.5 vs. 31.8, respectively; P=0.0017)
• Median PCA3 Scores were also higher in men with > 33% vs. ≤ 33% positive cores, > 50% vs. ≤ 50% maximum core involvement and PSA density > 0.15 vs. ≤ 0.15 ng/mL/cm3, although the differences were not statistically significant
• In men with a negative repeat biopsy at year 2, the PCA3 Score was predictive of biopsy outcome at year 4 (P=0.0002), whereas serum PSA (P=0.3281) and %free PSA (P=0.6782) were not predictive (Table). Men with a negative repeat biopsy at year 2 and a PCA3 Score > 35 had a 2-fold increased risk of a positive biopsy at year 4 (P=0.0188)
• In multivariate regression analysis, PCA3 was a strong independent risk factor for presence of PCa. Inclusion of PCA3 as a continuous variable in a multivariate model (including PCa risk factors age, family history, serum PSA, %free PSA and prostate volume) statistically significantly increased the AUC from 0.717 to 0.753 (P=0.0009). These results confirm that PCA3 can be used in combination with other clinical information to help guide prostate biopsy decisions
• The results of this validation study in the largest repeat biopsy cohort to date confirms the results of previous studies in smaller cohorts
• PCA3 may be detecting cancers that were missed by biopsy or PCA3 is related to precancerous states that progress

Figure. The median PCA3 Score was statistically significantly higher in men with a positive biopsy vs. those with a negative repeat biopsy

AUC ROC: Area Under the Receiver Operating Characteristic Curve

More information: Article at PubMed