Limited Incremental Diagnostic Value of Perilesional and Systematic Biopsies in PI-RADS 4–5 Lesions: A Retrospective Single-Center Study

Objective: This study aims to evaluate the additional diagnostic value of systematic (SBx) and perilesional biopsies (PBx) compared with targeted biopsy (TBx) in patients with mpMRI-detected PI-RADS 3-4–5 lesions. Methods: We performed a retrospective analysis of 208 men with PI-RADS ≥ 3 lesions who underwent mpMRI–ultrasound fusion biopsy at a single institution. Clinically significant prostate cancer (csPCa; ISUP ≥ 2) was identified in 155 patients (74.5%), who constituted the study cohort. All patients underwent a standardized biopsy protocol consisting of 3–5 TBx cores, 3 PBx cores sampled within a 10 mm radius of the index lesion, and 10 SBx cores using the KOELIS Trinity® system. Detection rates of csPCa and ISUP grade upgrading were analyzed and stratified by PI-RADS category. Results: TBx csPCa detection rates increased progressively with PI-RADS score: 39% for PI-RADS 3, 50% for PI-RADS 4, and 60% for PI-RADS 5 lesions. PBx showed a 42.5% detection rate of csPCa in PI-RADS 3 and 58% and 85.3% of csPCa in PI-RADS 4 and 5 respectively, whereas SBx detected 34.5% of csPCa in PI-RADS 3, 46% of csPCa in PI-RADS 4, and 60.5% of csPCa in PI-RADS 5. Despite these detection rates, PBx and SBx rarely provided clinically meaningful upgrading over TBx findings. ISUP grade upgrading occurred in only 7.3% of PBx cases and 1.8% of SBx cases in PI-RADS 5 lesions, with similarly low upgrading rates observed in PI-RADS 3–4 lesions. Conclusions: In patients with high-grade lesions like PI-RADS 4–5, TBx alone identifies the vast majority of csPCa, while SBx and PBx contribute minimal additional diagnostic or grading benefit. These findings support biopsy de-escalation strategies in high-risk mpMRI settings to reduce unnecessary sampling and procedure-related morbidity. On the other hand, in the PI-RADS 3 subgroup, omitting non-targeted sampling (SBx and/or PBx) may lead to underdiagnosis of higher-grade tumors not captured by TBx alone, potentially resulting in substantial changes in therapeutic strategy and, consequently, patient prognosis.