Natural History of PI‐RADS 3 Lesions on Serial Prostate mpMRI

OBJECTIVE: PI-RADS 3 lesions on prostate multiparametric MRI (mpMRI) are indeterminate findings with debated management. We evaluated their radiologic evolution on follow-up mpMRI and correlated imaging changes with biopsy outcomes. METHODS: We retrospectively identified 166 men with at least one PI-RADS 3 lesion on initial mpMRI and at least one follow-up mpMRI without intervening treatment. Lesions were classified at follow-up as regressed (downgraded to PI-RADS ≤ 2), stable (remained PI-RADS 3), or progressed (upgraded to PI-RADS 4-5). Lesions were stratified by zonal location. MRI-targeted biopsy results were reviewed when available (n = 64). RESULTS: On follow-up, 52% of lesions regressed, 29% remained stable, and 19% progressed. Progression was significantly more common for peripheral-zone lesions (25%) than transition-zone lesions (6%); no central-zone lesions progressed. Of the biopsied lesions, most yielded benign or low-grade pathology: 44% were benign, 47% were ISUP 1, 6% had high-grade PIN or ASAP, and only 3% harbored clinically significant prostate cancer (csPCa; ISUP ≥ 2). Both csPCa cases occurred in lesions that had progressed radiologically. Lesions with imaging progression were significantly more likely to yield cancer on initial or follow-up biopsy than stable/regressed lesions (83% vs 40%; p = 0.037). CONCLUSIONS: In this real-world cohort, most PI-RADS 3 lesions remained indolent: over half regressed, and 19% progressed. Biopsied lesions had a very low rate of csPCa (3%). These results suggest that surveillance with interval MRI rather than immediate biopsy may be a safe strategy for selected men with PI-RADS 3 lesions.