Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Prostate Biopsy in the Era of Lesion-focused...

The transperineal (TP) route is recommended for prostate biopsy due to its superior safety profile. However, randomized evidence comparing the TP and the transrectal (TR) routes was generated through combined targeted and systematic biopsy frameworks, now challenged by lesion-focused strategies, defined as the combination of targeted (TB) and perilesional (PB) sampling without distant systematic cores. This study aimed to reassess the diagnostic performance of TP versus TR biopsy with the recommended TB + PB scheme.

This prospective multicenter, observational study was conducted across 10 European institutions between January 2025 and June 2025. We included 912 men with at least one magnetic resonance imaging (MRI)-visible lesion (Prostate Imaging-Reporting and Data System version 2.1 ≥3) who underwent either TP or TR MRI-targeted biopsy according to predefined TB + PB protocols. The primary outcome was the detection rate of clinically significant prostate cancer (csPC; Gleason Grade [GG] Group ≥2).

TP biopsy detected more csPC than TR (48% vs 39%; OR [odds ratio]: 1.41, 95% CI [confidence interval]: 1.06-1.88; p = 0.017) without increasing the detection of insignificant PC (insPC) (18% vs 23%; p = 0.06). In multivariable mixed-effects analysis accounting for center-level clustering, the TP route remained independently associated with csPC detection (adjusted OR: 1.61, 95% CI: 1.17-2.23; p = 0.004). Limitations include limited power in selected subgroups and potential inter-center heterogeneity inherent to the observational design.

Within a standardized lesion-focused TB + PB framework, TP biopsy was independently associated with higher csPC detection without increasing insPC detection. This study focuses on diagnostic performance and does not provide direct comparative data on biopsy-related complications or patient-reported outcomes.