Development and validation of a novel multivariate risk score to guide biopsy decision for the diagnosis of clinically significant prostate cancer.

Objectives: Selecting patients suspected of having prostate cancer (PCa) for a prostate biopsy remains a challenge. Prostate-specific antigen (PSA)-based testing is hampered by its low specificity that often leads to negative biopsy results or detection of clinically insignificant cancers, especially in the 2-10 ng/mL range. The objective was to evaluate a novel diagnostic test called Proclarix incorporating thrombospondin-1 and cathepsin D alongside total and free PSA as well as age for predicting clinically significant PCa. Patients and methods: The test was developed following a retrospective study design using biobanked samples of 955 men from two reference centres. A multivariate approach was used for model development followed by validation to discriminate significant (grade group ≥2) from insignificant or no cancer at biopsy. The test specificity, positive predictive value (PPV) and negative predictive value (NPV) at a fixed sensitivity of 90% were compared to percent free PSA (%fPSA) alone. The number of avoidable prostate biopsies deemed to be representative of clinical utility was also assessed. Results: In the targeted patient population, the test displayed increased diagnostic accuracy compared to %fPSA alone. Application of the established model on 955 patients at a fixed sensitivity of 90% for significant disease resulted in a specificity of 43%, NPV of 95% and a PPV of 25%. This is in comparison to a specificity of 17%, NPV of 89% and PPV of 19% for %fPSA alone and had the potential to reduce the total number of biopsies needed to identify clinically significant cancer. Further, the test score correlated with significance of cancer assessed on prostate biopsy. Conclusions: The Proclarix test can be used as an aid in the decision-making process if to biopsy men in this challenging patient population. The use of the test could reduce the number of biopsies performed avoiding invasive procedures, anxiety, discomfort, pain and complications.