BACKGROUND AND OBJECTIVE: Uptake of active surveillance for patients with Gleason grade group (GG) 2 prostate cancer (PCa) remains low. Magnetic resonance imaging (MRI) before biopsy would allow better patient selection, but there are no published data on this strategy. Our aim was to report one of the first European AS series of patients with GG 2 PCa selected via MRI before image-guided biopsy. METHODS: This multicenter study enrolled patients with GG 2 PCa managed with AS between 2016 and 2024 in ten reference centers in France, Spain, Italy, Switzerland, and Germany. Patients deemed unsuitable for curative treatment (ie, watchful waiting) were excluded. The primary endpoint was metastasis-free survival. KEY FINDINGS AND LIMITATIONS: A total of 139 patients with GG 2 PCa were included. Baseline MRI revealed a lesion with a Prostate Imaging-Reporting and Data System score of 4-5 in 81 patients (59%). Median event-free follow-up was 38 mo (interquartile range 20-63). Two cases of metastasis were observed, and there were no deaths due to PCa. The estimated 3-yr metastasis-free survival rate was 98.1% (95% confidence interval 95.5-100%). Overall, 56 patients underwent definitive treatment and 26 were reclassified as having GG 3 PCa during follow-up. Among the 28 patients who underwent radical prostatectomy, final pathology revealed adverse features (GG 3 and/or pT3a) in 13 cases (46%), but very aggressive disease (GG ≥4 and/or ≥pT3b and/or pN1) was noted in only two cases (7%). There were no statistically significant differences in outcomes between groups that did and did not meet the European Association of Urology inclusion criteria for AS (all log-rank tests p >
0.05). CONCLUSIONS AND CLINICAL IMPLICATIONS: In the era of prebiopsy MRI and image-guided biopsy, AS is a safe management option for selected patients with GG 2 PCa. Future studies should focus on redefining current inclusion criteria for AS in the targeted biopsy era, as many patients with GG 2 PCa are at low absolute risk of distant progression.