Background and Objective MRI-driven active surveillance (AS) is increasingly used for prostate cancer (PCa) management. To determine the oncological safety of contemporary, MRI-driven AS and identify patients at higher risk of AS failure.

Methods This retrospective cohort study included AS patients with MRI-localised PCa from three US and UK centres. The primary outcome was AS failure, a composite of PCa-specific mortality, metastasis, progression to ≥GG4, or post-treatment biochemical recurrence. The secondary outcome was disease progression, defined as histological progression to GG3 or progression to locally advanced disease. Hazard ratios (HRs) were estimated using multivariable Cox models, with multiplicity-adjusted log-rank tests comparing event-free survival across subgroups.

Key Findings and Limitations 719 patients (median follow-up 5.2 years) were included. Of those, 629 (87%) had stable disease; 36 (5%) experienced AS failure, including 8 (1%) cases of metastasis and no PCa-related deaths; 54 (8%) had disease progression. Cribriform GG2 histology was the strongest predictor of AS failure (HR 12.7 95% CI, 4.8–33.6; P < 0.001), followed by tumor MRI-visibility (HR 5.0; 95% CI, 1.5-16.5; P = 0.009) and non-cribriform GG2 histology (HR 3.4; 95% CI, 1.6-7.0; P = 0.001). MRI-invisible, non-cribriform GG2 and all GG1 tumors had comparable event-free survival (Padj > 0.05 for both outcomes). The study is limited by retrospective design.

Conclusions and clinical implications Contemporary MRI-driven AS is safe, including for patients with non-cribriform GG2 tumours, particularly those that are MRI-invisible. Conversely, patients with cribriform GG2 disease are at increased risk of AS failure and therefore warrant upfront treatment.

The authors have declared no competing interest.

The study was funded by the National Institute for Health and Care Research (NIHR), UK, and Cancer Research UK Cambridge Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. N.S. acknowledges support from Emmanuel College, Cambridge. A.Y.W. is supported by the Urological Malignancies Programme of the Cancer Research UK Cambridge Centre (C9685/A25177) and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). TMS acknowledges support from the Prostate Cancer Foundation (24CHAL03).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This retrospective cohort study was approved by the institutional review boards of the Cambridge University Hospitals (CUH/18/3592), University of California San Diego (191878), and University of Texas San Antonio (HSC20150160H).

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