Role of PCA3 as a primary screening tool
In the European Randomised Study of Screening for Prostate Cancer (ERSPC) trial, PCA3 was assessed as a first line-screening test.40 While the positive predictive values of a PCA3 score of 10 or higher and PSA value of 3 ng/mL or greater were comparable (17.1 vs. 18.8), PCA3 missed fewer cancers (32% vs. 65%), and most interestingly, detected more serious cancers (26% vs. 58%).
It is important to note that these findings must be confirmed in unscreened PSA naïve patients to best assess any future role of PCA3 as a primary screening tool.
In April 2013, the American Urological Association (AUA) released updated guidelines on early detection of PCa.41 The panel recognized that the PCA3 test plays a role as a secondary screening test (after PSA screening) and that the test can be used as an adjunct for informing decisions about the need for a PBx or repeat biopsy.
Several recently constructed and externally validated PCA3-based biopsy nomograms (e.g., the Prostate Cancer Prevention Trial Risk Calculator) have shown that incorporation of PCA3 with other established risk factors (PSA, age, DRE, biopsy history, prostate volume) improves diagnostic accuracy and helps identify patients with clinically significant disease who may benefit from active treatment.42,43
Recently, TMPRSS2-ERG gene fusion and its role in prostate tumorogenesis has been the point of interest in PCa research. So far, research has shown that the combination of TMPRSS2-ERG with PCA3 may improve overall sensitivity for PCa detection.
Hessels and colleagues reported increased sensitivity from 62% (PCA3 alone) to 73% (TMPRSS2-ERG + PCA3) without compromising specificity for PCa detection.44 Salami and colleagues reported 80% sensitivity and 90% specificity to detect PCa using a combination of serum PSA, PCA3, and TMPRSS2-ERG.45
At the AUA annual meeting in 2013, Jones et al. reported on the utility of PCA3 and TMPRSS2:ERG in a cohort of 638 men prior to an initial biopsy.46 When both assays were combined into risk groups, substantial differences in probability of cancer detection were observed between the low (14%) and high (84%) risk groups.
Although not studied in a prospective randomized trials, these early investigations support that using a combination of PCA3 and TMPRSS2:ERG may be beneficial in not only selecting patients for repeat biopsy, but improving prediction of indolent versus clinically significant disease as well.