Transperineal versus Transrectal Prostate Biopsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To compare the safety and diagnostic performance of transperineal (TP) versus transrectal (TR) ultrasound-guided prostate biopsies using only data from randomized controlled trials (RCTs). A systematic search was performed in multiple databases up to May 2025. We included only RCTs comparing TP and TR approaches in men undergoing MRI-targeted prostate biopsies. Meta-analysis was conducted using odds ratios (OR) and 95% confidence intervals (CI) for categorical outcomes. The primary endpoints were cancer detection rate and postbiopsy infection rate. Secondary outcomes included urinary retention, bleeding, pain, and complications stratified by the Clavien-Dindo system. Study quality and certainty of evidence were assessed using the Cochrane ROB2 and GRADE tools. Four RCTs encompassing 2682 patients (TP: 1323; TR: 1359) were included. No significant differences were observed in overall prostate cancer detection rates (OR 1.03, 95% CI, 0.79-1.36) or detection of anterior lesions (OR 1.01, 95% CI, 0.41-2.45). Similarly, no differences were found in bleeding (OR 1.14, 95% CI, 0.66-1.95), urinary retention (OR 1.01, 95% CI, 0.50-2.04), total infections (OR 1.02, 95% CI, 0.77-1.35), or severe infections (OR 2.17, 95% CI, 0.97-4.88). Mild pain was more frequent in the TP group (OR 1.56, 95% CI, 1.20-2.03), while moderate to severe pain did not differ significantly (OR 0.65, 95% CI, 0.39-1.07). Transperineal and transrectal MRI-fusion-guided biopsy approaches demonstrated equivalent diagnostic accuracy and safety profiles. While the transperineal route was associated with slightly greater mild discomfort, cancer detection and complication rates were comparable. The selection of approach should be guided by principles of antimicrobial stewardship, patient preference, and institutional expertise.