BackgroundGranulomatous prostatitis is a medical condition that may mimic prostate cancer. PurposeGranulomatous prostatitis resulting from BCG-exposure can confound the diagnosis of prostate cancer based on prostate imaging and data system (PI-RADS) classification observed on multiparametric prostate magnetic resonance imaging (mpMRI). Study type, Population, Assessment and Statistical TestsA cohort study was conducted, enrolling consecutive males at risk for prostate cancer who underwent an mpMRI-targeted prostate biopsy between February 2016 and August 2023. The focus of the study was on prior BCG-exposure as adjuvant treatment for non–muscle-invasive urothelial carcinoma within the 3 years prior the magnetic resonance imaging (MRI). Exclusion criteria were a prior androgen deprivation therapy, prostate surgery or radiation, and BCG-exposure occurring more than 3 years and less than 3 months before the MRI. Chi-square, logistic-regression, statistical association, and homogeneity tests were used. ResultsTotal 712 patients, 899 biopsied lesions (218 PI-RADS 3, 521 PI-RADS 4 and 160 PI-RADS 5) and 20 patients with 30 lesions within the BCG-exposed cohort. Chi-square and logistic-regression tests showed an association between PI-RADS with malignancy and significant tumor (ST), considering PI-RADS3 as the reference (OR: 4.9 [95% CI, 3.4-7.1] for PI-RADS4 and OR: 21.7 [95% CI, 12.4-37.8] for PI-RADS5 for malignancy, and OR: 5.3 [95% CI, 3.2-8.7] for PI-RADS4 and OR: 16.5 [95% CI, 9.4-28.9] for PI-RADS5 regarding ST). A statistically significant negative association was demonstrated between malignancy and ST with respect to BCG-exposure (OR: 0.15 [95% CI, 0.06-0.39] and OR: 0.39 [95% CI, 0.15-1.0], respectively). Statistically significant risk-difference for malignancy in patients nonexposed to BCG regarding those exposed was 45% (61.6% vs. 16.7%) for PI-RADS4, and 68.5% (90.7% vs. 22.2%) and 42.7% (64.9% vs. 22.2%) concerning malignancy and ST for PI-RADS5, respectively. Data ConclusionsGranulomatous prostate reaction caused by BCG-exposure acts as confounding factor for prostate MRI interpretation. The risk of malignancy and significant tumor on targeted biopsy to PI-RADS 3, 4 and 5 is notably lower in exposed patients.