Transperineal MRI-US Fusion-Guided Biopsy with Systematic Sampling for Prostate Cancer: Diagnostic Accuracy and Clinical Implications Across PI-RADS

<b>Background/Objectives</b>: Magnetic resonance imaging (MRI) and MRI-ultrasound (US) fusion-targeted biopsy have improved prostate cancer diagnosis, particularly for clinically significant disease. However, the added value of combining systematic biopsy with targeted biopsy remains debated. This study aimed to evaluate the diagnostic accuracy of MRI-US fusion-targeted and systematic transperineal biopsies in detecting prostate cancer and explore the correlation between PI-RADS score and histology. <b>Methods</b>: We retrospectively analyzed 356 patients with 452 MRI-detected lesions who underwent both MRI-US fusion-targeted and transperineal systematic biopsies between 2020 and 2023. Clinically significant prostate cancer (csPCa) was defined as International Society of Urological Pathology (ISUP) grade ≥ 2. Diagnostic performance metrics (sensitivity, specificity, and accuracy) were calculated for each technique using the combined result as a reference. Subgroup analysis was performed for patients under active surveillance. <b>Results</b>: Prostate cancer was diagnosed in 323 of 452 lesions (71%) and csPCa in 223 lesions (49%). Targeted biopsy demonstrated higher sensitivity (93.7%) and accuracy (79.9%) than systematic biopsy (85.7% sensitivity and 77.6% accuracy), although systematic biopsy provided slightly higher specificity. Systematic biopsy alone identified 8.2% of PCa cases missed by targeted biopsy and upgraded 9.9% of lesions to csPCa. csPCa detection increased with PI-RADS score (23% in PI-RADS 3 and 73% in PI-RADS 5). In active surveillance patients, csPCa was found in 65% of lesions. <b>Conclusions</b>: MRI-US fusion-targeted biopsy improves csPCa detection, but systematic biopsy remains valuable, especially for identifying additional or higher-grade disease. The combined approach provides an optimal diagnostic yield, supporting its continued use in both initial and repeat biopsy settings.