278 Background: The use of multi-parametric magnetic resonance imaging (mpMRI) has been a significant advance in the diagnosis of prostate cancer (PCa) recommended in a number of guidelines. There are considerable resource implications in scanning all men at risk of PCa. Furthermore, a significant number of mpMRIs are reported as indeterminate, leading to unnecessary biopsies. Proclarix is a CE-marked test based on two novel biomarkers, thrombospondin 1 (THBS1) and cathepsin D (CTSD), combined with PSA and age. A software algorithm returns a risk score that can be used as an aid in the identification of clinically significant PCa (any Grade Group 2 or greater). We aimed to assess the potential of Proclarix to identify those men who could safely avoid an upfront mpMRI or those men who could avoid biopsy when the mpMRI was indeterminate. Methods: Proclarix was correlated retrospectively with diagnostic data from 282 men recruited in the INNOVATE study (NCT02689271). INNOVATE involved men undergoing mpMRI followed by targeted and systematic biopsies in those with a suspicious mpMRI. Results: Median age and PSA were 66 (IQR 59-70) and 5.4 (3.8-7.8) ng/mL. 182 (65%) men underwent biopsy and 78 (43%) had GG≥2 PCa. Application of Proclarix in all 282 men undergoing mpMRI resulted in a sensitivity for clinically significant PCa (GG≥2) of 91%, a negative predictive value (NPV) of 92% and 38% specificity. When normalized to the same sensitivity of 91%, %fPSA resulted in both lower NPV (89%) and specificity (28%) when compared to Proclarix. 144 (51%) men had an indeterminate mpMRI of whom 84 (58%) had a biopsy and 13 (15%) had GG≥2 PCa. In these men, Proclarix had an NPV of 100%, at 100% sensitivity and a specificity of 34%. When results were compared using equal sensitivity, PSA density (cut-off 0.05 ng/mL), which is frequently used to inform the need for biopsy, had 10% specificity. Conclusions: The use of Proclarix could potentially allow 38% of men to avoid undergoing an mpMRI. In men with an indeterminate mpMRI, Proclarix could allow one-third to safely avoid biopsies without missing any clinically significant cancer.