Efficacy of Prostate Biopsies via Transperineal and Transrectal Routes for Significant Prostate Cancer Detection: A Multicenter Paired-Matched Study.

: A transperineal approach to prostate biopsy is now recommended to reduce the risk of infectious complications associated with the transrectal route. Our aim is to compare the efficacy of transrectal- and transperineal-guided biopsies involving the magnetic resonance imaging (MRI) of index lesions in detecting significant prostate cancer (sPCas), and to evaluate the role of systematic biopsies. : In a prospective and multicenter trial conducted in an opportunistic early detection program for sPCa in Catalonia (Spain), between 2021 and 2023, 4029 men suspected of having PCa underwent multiparametric MRI followed by guided and systematic biopsies. From this cohort, we retrospectively selected 1376 men with reports of the size and localization of their index lesions. A matched group of 325 pairs of men subjected to transrectal and transperineal biopsy were chosen to account for confounding variables. We compared sPCa detection rates determined via index lesions and systematic biopsies, as well as by lesion localization. : Transperineal and transrectal biopsies detected sPCa in 49.5% vs. 40.6% overall ( = 0.027), 44.6% vs. 30.8% from index lesions ( = 0.001), and 24.3% vs. 35.1% from systematic biopsies ( = 0.003). SPCa detection rates were higher in transperineal biopsies across all index lesion localizations, with significant increases in the anterior zone (47.8% vs. 20.8% at the mid-base, = 0.039, and 52.9% vs. 24.2% at the apex, = 0.024) and central zone (33.3% vs. 5.9%, = 0.003). With regards to SPCa detected only in systematic biopsies, 10.5% of cases were detected in transrectal biopsies and 4.9% of cases were detected in transperineal biopsies ( = 0.012). : Targeted biopsies conducted via the transperineal route showed higher sPCa detection rates than transrectal biopsies, particularly for anterior and apical lesions, with systematic biopsies showing reduced utility.