Clinical utility of the (-2)proPSA and evaluation of the evidence: A systematic review

Background: Diagnostic studies usually provide important information about the analytical and diagnostic performances. We investigated the clinical utility of (-2)proPSA in identifying patients with prostate cancer (PCa). Methods: We performed electronic searches in five data-bases as well as a list of reference literature. Studies were included if they evaluated the diagnostic accuracy of (-2) proPSA in men with PSA value ranged from 2.0 to 10 mu g/L. We also analyzed data about total PSA (tPSA), %(-2)proPSa, freePSA (fPSA), its percentage (% fPSA) and the prostate health index (phi). The selection of the studies, the screening of the full texts and the data extraction, as well as the assessment of risk of bias using the QUADAS-2 tool were conducted independently by two authors. Grading the quality of the evidence was carried out according to the GRADE method. The random effects model was used for the meta-analyses. Results: We included 17 studies, including 6912 patients. The pooled sensitivity of (-2) proPSA was 90% and the summary specificity was 13%. The tPSA sensitivity and specificity were 89% and 25%, respectively. Considering (-2) proPSA, 225 men out of 1000 have been identified having PCa true positives (TP). However, 652 persons have been incorrectly identified and undergo biopsy. The majority of studies were judged to carry a moderate risk of bias. Therefore, the overall quality of evidences was deemed to be low. Conclusions: The (-2)proPSA could be useful to identify men at risk of PCa, but its accuracy still remains uncertain and the level of evidence does not support an improved clinical utility.