PROPOSe: A Real-life Prospective Study of Proclarix, a Novel Blood-based Test to Support Challenging Biopsy Decision-making in Prostate Cancer.

Abstract Background Prostate-specific antigen (PSA)-based detection of prostate cancer (PCa) often leads to negative biopsy results or detection of clinically insignificant PCa, more frequently in the PSA range of 2–10 ng/ml, in men with increased prostate volume and normal digital rectal examination (DRE). Objective This study evaluated the accuracy of Proclarix, a novel blood-based diagnostic test, to help in biopsy decision-making in this challenging patient population. Design, setting, and participants Ten clinical sites prospectively enrolled 457 men presenting for prostate biopsy with PSA between 2 and 10 ng/ml, normal DRE, and prostate volume ≥35 cm3. Transrectal ultrasound–guided and multiparametric magnetic resonance imaging (mpMRI)-guided biopsy techniques were allowed. Outcome measurements and statistical analysis Serum samples were tested blindly at the end of the study. Diagnostic performance of Proclarix risk score was established in correlation to systematic biopsy outcome and its performance compared with %free PSA (%fPSA) and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) as well as Proclarix density compared with PSA density in men undergoing mpMRI. Results and limitations The sensitivity of Proclarix risk score for clinically significant PCa (csPCa) defined as grade group (GG) ≥2 was 91% (n = 362), with higher specificity than both %fPSA (22% vs 14%; difference = 8% [95% confidence interval {CI}, 2.6–14%], p = 0.005) and RC (22% vs 15%; difference = 7% [95% CI, 0.7–12%], p = 0.028). In the subset of men undergoing mpMRI-fusion biopsy (n = 121), the specificity of Proclarix risk score was significantly higher than PSA density (26% vs 8%; difference = 18% [95% CI, 7–28%], p  Conclusions In a routine use setting, Proclarix accurately discriminated csPCa from no or insignificant PCa in the most challenging patients. Proclarix represents a valuable rule-out test in the diagnostic algorithm for PCa, alone or in combination with mpMRI. Patient summary Proclarix is a novel blood-based test with the potential to accurately rule out clinically significant prostate cancer, and therefore to reduce the number of unneeded biopsies.