Predicting Active Surveillance Failure for Patients with Prostate Cancer in the Magnetic Resonance Imaging Era: A Multicentre Transatlantic Cohort Study.

Background and objective: Magnetic resonance imaging (MRI)-driven active surveillance (AS) is increasingly used for management of prostate cancer (PC). The aim of our study was 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 PC from three US and UK centres. The primary outcome was AS failure, which was defined as a composite of PC-specific mortality, metastasis, progression to grade group (GG) ≥4, or post-treatment biochemical recurrence. The secondary outcome was disease progression, defined as histological progression to GG 3 or progression to locally advanced disease. Hazard ratios (HRs) were estimated using multivariable Cox models, and multiplicity-adjusted log-rank tests were applied to compare event-free survival across subgroups.

Key findings and limitations: The study cohort comprised 719 patients with median follow-up of 5.2 yr. Of these patients, 629 (87%) had stable disease; 36 (5%) experienced AS failure, including eight (1%) cases of metastasis and no PC-related deaths; and 54 (8%) had disease progression. Cribriform GG 2 histology was the strongest predictor of AS failure (HR 12.7, 95% confidence interval [CI] 4.8-33.6; p < 0.001), followed by tumour MRI visibility (HR 5.0, 95% CI 1.5-16.5; p = 0.009) and noncribriform GG 2 histology (HR 3.4, 95% CI 1.6-7.0; p = 0.001). Event-free survival was comparable for MRI-invisible noncribriform GG 2 and all GG 1 tumours (adjusted p > 0.05 for both outcomes). The study is limited by its retrospective design.

Conclusions and clinical implications: Contemporary MRI-based AS for PC is safe for suitable patients, including men with noncribriform GG 2 tumours, particularly those that are MRI-invisible. Conversely, patients with cribriform GG 2 disease are at higher risk of AS failure, so consideration of upfront treatment is warranted for this subgroup.