Transperineal Versus Transrectal Biopsy for Prostate Cancer Diagnosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background and objective: There has been debate for decades whether transperineal prostate biopsy (TP-Bx) or transrectal biopsy (TR-Bx) is the optimal route. Randomized controlled trials (RCTs) conducted in the contemporary era provide new evidence for reassessment of the comparative infectious risks and diagnostic performance, particularly relevant given rising antibiotic resistance and evolving prostate cancer (PC) diagnostic paradigms. Our aim was to compare infectious complications, detection of clinically significant PC (csPC), and other biopsy-related outcomes between TP-Bx and TR-Bx in men with suspected PC undergoing biopsy in the multiparametric magnetic resonance imaging (mpMRI) era. Methods: A systematic literature search (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, and ClinicalTrials.gov) was conducted on April 1, 2025 in accordance with PRISMA guidelines. RCTs comparing TP-Bx and TR-Bx published after 2010 were included. Data were independently extracted by two reviewers using a standardized protocol (PROSPERO CRD42024522857). Risk of bias was assessed using the updated Cochrane tool. We performed a Bayesian random-effects meta-analysis, using models specifically suited for few-study settings and rare events. Sensitivity analyses were performed. The primary outcome was the infectious complication rate. Secondary outcomes included detection of csPC and non-clinically significant PC (ncsPC), urinary retention, bleeding, and patient-reported pain. Key findings and limitations: Five RCTs involving 3072 men were included (1547 TP-Bx, 1525 TR-Bx). The vast majority were Bx-naïve and underwent mpMRI-targeted Bx. TP-Bx was associated with lower risk of infectious complications (pooled odds ratio [pOR] 0.38, 95% credible interval [CrI] 0.11-0.90), despite no antibiotic prophylaxis in this arm. Results also suggest a lower risk of bleeding requiring intervention with TP-Bx (pOR 0.54, 95% CrI 0.23-1.14), although the estimates were imprecise. There was no evidence of a difference in detection of csPC (pOR 1.01, 95% CrI 0.65-1.51) or ncsPC (pOR 1.12, 95% CrI 0.63-2.18), or in acute urinary retention (pOR 0.66, 95% CrI 0.26-1.58). Two studies assessing pain reported higher post-Bx pain scores for TP-Bx, and two studies reported slightly longer operating times, although these differences were of uncertain clinical relevance. Conclusions and clinical implications: TP-Bx offers lower infection rates with no antibiotic prophylaxis needed and equivalent PC detection in comparison to TR-Bx, despite minimal increases in discomfort and procedure time. When feasible, TP-Bx should be considered the preferred Bx approach.