Proclarix’ performance in ruling out patients with no or indolent prostate cancer: evaluation in a Danish population

PSA testing is widely used for the early detection of prostate cancer (PCa), but its low specificity leads to overdiagnosis and unnecessary interventions. Proclarix, a novel blood test combining serum levels of prostate specific antigen (PSA), percentage of free PSA (%fPSA), Cathepsin D (CTSD) and Thrombospondin 1 (THBS1) with age into a risk score, aims to improve risk stratification by predicting clinically significant PCa (csPCa). This study evaluated its diagnostic performance in a Danish population using retrospective serum samples collected consecutively from patients with suspected PCa. Proclarix’ ability to reduce biopsies and detection of clinically insignificant PCa (ciPCa, defined as Grade Group < 2) was assessed in men with a PSA 2–10 ng/ml and a prostate volume of ≥ 35 ml (targeted population) compared with the percentage of free PSA (%fPSA) and the European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC-RC). The secondary analysis included the performance of Proclarix’ and Proclarix density compared with the %fPSA and PSA density (PSA-D) in a broader population with a PSA 2–20 ng/ml regardless of both prostate volume and DRE (extended population). Proclarix score is considered negative when it’s below the cutoff 10%. In the targeted population (n = 373), a negative Proclarix test significantly reduced the probability of csPCa from 27% (pretest) to 5% (posttest, 95%CI: 0–10%), (p < 0.028) outperforming %fPSA (posttest 14%, 95%CI: 4–24%) and ERSPC-RC (posttest 20%, 95%CI: 4–36%). For the diagnosis of csPCa, Proclarix had a significantly (p < 0.01) greater specificity of 22% (95%CI: 17–27%) at 97% sensitivity (95%CI: 94–100%) and 95% NPV (95%CI: 90–100%) than did %fPSA and the ERSPC-RC, with 14% (95%CI: 10–18%) and 7% (95%CI: 4–11%) specificity, respectively. In the extended population (n = 656), Proclarix density had significantly (p < 0.01) greater specificity (39%, 95%CI: 35–44%) than did PSA-D (32%, 95%CI: 27–36%) at an equal sensitivity of 90%. Proclarix reduces prostate biopsies and ciPCa detection while maintaining a low risk of missing csPCa.