Multiparametric magnetic resonance imaging has improved risk stratification and lesion-directed sampling in suspected prostate cancer. MRI–ultrasound fusion biopsy targets MRI-visible lesions, whereas systematic biopsy provides non-targeted glandular sampling. This study aimed to compare the diagnostic yield of fusion and systematic biopsy in a single-center paired cohort and to explore biopsy-to-surgical pathology concordance in operated patients. This retrospective study included 138 men who underwent both fusion-targeted and systematic biopsy during the same diagnostic work-up. The primary endpoint was overall prostate cancer detection; secondary endpoints included clinically significant prostate cancer detection, discordance between methods, PI-RADS-stratified detection, complications, and exploratory surgical pathology findings. Clinically significant cancer was defined as a Gleason score ≥3+4 / ISUP Grade Group ≥2. Fusion biopsy detected prostate cancer in 65/138 men (47.1%) versus 56/138 (40.6%) for systematic biopsy; combined biopsy detected cancer in 72/138 (52.2%). Fusion-only detection occurred in 16 patients (11.6%) and systematic-only detection in 7 (5.1%). The paired difference for overall cancer detection did not reach statistical significance (exact McNemar P = 0.093). Clinically significant prostate cancer was detected in 37/138 men (26.8%) by fusion biopsy and 35/138 (25.4%) by systematic biopsy (P = 0.815). Detection rates increased with PI-RADS category and were highest in PI-RADS 5 lesions. Surgical pathology was available in 45 patients; upgrading occurred in 21 (46.7%) and adverse pathology in 18 (40.0%). Fusion biopsy showed a numerically higher overall detection rate, particularly in PI-RADS 5 lesions, while systematic biopsy retained complementary value. These findings support a combined targeted and systematic biopsy strategy in selected patients. Current evidence also suggests that careful antibiotic stewardship is a safe approach in the management of office-based transrectal prostate biopsy.
