BACKGROUND: Multiparametric MRI (mpMRI) and fusion-targeted biopsy (TB) have improved the detection of clinically significant prostate cancer (csPCa)
however, it remains unclear whether secondary lesions (SLs) identified on mpMRI must also be biopsied in addition to the index lesion (IL). Currently, American Urological Association and European Association of Urology guidelines suggest biopsying all lesions, but supporting data are sparse. This study examines whether including SL biopsies provides additional value in csPCa detection compared to IL biopsy alone when systematic biopsy (SB) is also performed. METHODS: Men with multiple PI-RADS ≥ 3 lesions on mpMRI who underwent prostate biopsy were retrospectively identified. The primary analysis compared csPCa detection rates from SB and IL TB, with or without SL TB. Secondary analyses assessed the impact of prostate-specific antigen (PSA) density and SL PI-RADS scores on csPCa detection. Sensitivity analyses were performed to investigate the robustness of findings. RESULTS: Among 73 men, csPCa detection rate was 47% with SB and IL biopsy alone and improved to 52% with SL biopsies included (p = 0.62). Secondary analyses showed no significant differences in csPCa detection based on PSA density or SL PI-RADS scores. Two of three sensitivity analyses supported the primary findings. CONCLUSIONS: Biopsying SLs does not significantly increase csPCa detection rates compared to IL biopsy alone when SB is also performed. This supports the notion that SL biopsies can be safely omitted without compromising clinical outcomes, thereby potentially reducing patient discomfort and procedural costs, and may inform future guideline development and revisions.