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 < 0.001), and at equal sensitivity of 97%, Proclarix density had an even higher specificity of 33% [95% CI, 23-43%].

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.

Keywords: Biomarkers; Biopsy; Cathepsin D; Diagnosis; Multiparametric magnetic resonance imaging; Proclarix; Prostate cancer; Prostate-specific antigen; Thrombospondin-1.