MRI-targeted biopsy with index lesion ipsilateral or bilateral systematic biopsy in prostate cancer: A multicenter, paired, noninferiority, observational trial.

375 Background: Index lesion-focused ipsilateral systematic biopsy (iSB) may potentially replace systematic biopsy (SB) in the MRI-targeted biopsy plus systematic biopsy (TB+SB) paradigm for prostate cancer, but prospective multicenter validation is limited. Methods: This prospective multicenter trial (NCT06584279) enrolled biopsy-naïve men with prostate imaging reporting and data system (PI-RADS) ≥4 lesions or PI-RADS 3 plus prostate-specific antigen (PSA) density ≥0.15 ng/mL/cm 3 . All underwent MRI-targeted biopsy (≥ 2 cores/lesion) with 12-core SB. Through core-level reclassification, we simulated TB+iSB (targeted cores + ipsilateral systematic cores from the index lesion lobe). Primary outcome was the cancer detection rate (CDR) of clinically significant prostate cancer (csPCa; Grade Group ≥2) with a noninferiority margin of -3%. The secondary outcomes included clinically insignificant prostate cancer (cisPCa; Grade Group = 1) detection and pathological concordance after radical prostatectomy. Results: 564 men (median age, 69 years; median PSA, 7.3 ng/mL) were included. TB+iSB demonstrated a noninferior csPCa CDR versus TB+SB (40.78% vs 42.38%; difference, -1.6%, 95% CI [-2.69, -0.5]), with the 95% CI lower bound not exceeding the -3% noninferiority margin. The CDR of cisPCa with TB+iSB was slightly lower than that with TB+SB (13.83% vs 14.36%; difference, -0.53%, 95% CI [-2.0, -0.92]). Among the 189 surgical patients, pathological concordance was similar between TB+iSB (54.0%) and TB+SB (55.6%); upgrade and downgrade rates were also comparable. Conclusions: This study establishes TB+iSB as a noninferior alternative to TB+SB for csPCa detection, supporting its adoption in MRI-guided biopsy protocols to reduce the procedural burden without compromising diagnostic accuracy. Clinical trial information: NCT06584279 .