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• With 3D Navigo™ system the targeted approach outperforms the systematic one. • The systematic biopsy detects high risk disease and should not be omitted. • Biopsy may be omitted when no visible lesion is demonstrated on mpMRI. The introduction of multi parameter magnetic resonance imaging (mpMRI) of the prostate in combination with MRI/TRUS fusion and systematic biopsy resulted in improved detection of prostate cancer. The aim of the current study was to document the performance of MRI/TRUS fusion biopsy of the prostate using the Navigo™ software in a contemporary cohort of patients from nonreferral centers. We performed a two centers prospective data collection (2014–2020) for men with clinically suspected Pca and patients on active surveillance for low-risk Pca that were referred for TRUS biopsy after performing mpMRI of the prostate with a visible lesion. The primary outcome was detection of clinically significant cancer (csPca) defined as ISUP grade group ≥2. Patients were stratified according to biopsy technique and PI-RADS category. The study group included 236 patients of whom 129 (54.9%) were diagnosed with Pca and 82 (34.7%) with csPca (GG ≥ 2) on combined biopsy. The overall detection of csPca was 31% for targeted vs. 25.4% for systematic biopsy with an absolute difference of 5.6% in favor of the fusion technique. No significant difference between the two techniques was observed for detection of benign prostate or GG1 disease. The improved performance of the targeted approach was noted only in patients with PI-RADS 4 and 5 lesions. Of the patients with csPca 10 (12%) were diagnosed only by the systematic biopsy while 20 (24%) were detected only in the fusion biopsy. Systematic biopsy of prostate lobe without MRI lesion detected only 2 cases (∼1%) with high grade disease. Detection of csPca by mpMRI/TRUS fusion biopsy using the 3D Navigo™ system is feasible. The targeted approach outperforms the systematic one, however the later technique also detects high risk disease and should be included in the biopsy procedure. The overall detection rate (34.9%) of clinically significant prostate cancer by both targeted and systematic sampling is relatively low. [ABSTRACT FROM AUTHOR]