Prospective Evaluation of Proclarix® Test to Improve Risk Stratification in Men Scheduled for MpMRI and Prostate Biopsy in Cantonal Hospital Aarau

Hypothesis and primary objective The aim of the study is the implementation of new biomarkers (Proclarix) in order to increase the sensitivity and specificity of PSA-based PCa early detection avoiding unnecessary prostate biopsies thus decreasing the associated morbidity (infections, bleeding, urinary retention, etc.). PSA values, Proclarix and mpMRI findings will be correlated with the results of the prostate biopsy in order to improve patient selection for future biopsies in order to avoid unnecessary prostate biopsies, but still be able to detect relevant carcinomas at an early stage. The null hypothesis in our observational study is the lack of superiority in PCa early detection when using the Proclarix over PSA alone. Primary and secondary endpoints The primary endpoint is the sensitivity and specificity of the Proclarix risk score in relation to the prediction of significant prostate cancer (Gleason score \>7) in the prostate biopsy. These parameters should be compared to PSA, %fPSA and the mpMRI findings. The secondary endpoints: The correlation of the data collected from mpMRI (according to PI-RADS) to the biopsy results. The combination of clinical parameters, PSA values, Proclarix, mpMRI and pathology results in order to develop predictive risk stratification tool (e.g. risk score or nomogram) for PCa. Determination of the analytical performance of the recently introduced Alinity i-Systems for PSA determination compared to the Architect i2000sr system (Abbott Laboratories) in terms of precision and validation of the reference interval according to the CLSI guidelines. The study design of this single-center, single-arm, non-blinded prospective study includes the collection and storage of 40 ml serum from all patients who meet the inclusion criteria according to point 3.1 and are planned for a prostate biopsy as part of the routine clinical PCa workup with mpMRI of the prostate starting from September 2021. While participants are going to be recruited in prospective manner and asked for their consent, the Proclarix biomarkers as well as %fPSA and tPSA will be determined post-interventionally (analog to the PROPOSE trial). According to the power analysis, 480 samples are necessary to achieve a 25%, statistically significant improvement in the negative predictive value of Proclarix compared to MPSA, assuming that 50% or more of all patients have a positive biopsy. The mpMRI findings and biopsy results should be analyzed by frequency distribution and compared by standard statistical testing.The design of a risk stratification tool should be achieved by means of logistic regression analysis. Various parameter combinations should be compared by standard statistical testing.In order to evaluate the performance of the recently introduced Alinity i system for PSA assays in terms of precision and correlation compared to the Architect i2000sr system (Abbott Laboratories) and to validate the reference interval according to CLSI guidelines, approximately 100 serum samples will be included for the comparison of the two methods by means of standard statistical testing. SPSS v.24 standard statistical package will be used for the most of the data analysis. The statistical analysis will be performed with assistance of external statistician. P-value \<0.05 or diverging boundaries of 95% confidence intervals will be considered as statistically significant.