Developing machine learning algorithms for dynamic estimation of progression during active surveillance for prostate cancer.

Active Surveillance (AS) for prostate cancer is a management option that continually monitors early disease and considers intervention if progression occurs. A robust method to incorporate "live" updates of progression risk during follow-up has hitherto been lacking. To address this, we developed a deep learning-based individualised longitudinal survival model using Dynamic-DeepHit-Lite (DDHL) that learns data-driven distribution of time-to-event outcomes. Further refining outputs, we used a reinforcement learning approach (Actor-Critic) for temporal predictive clustering (AC-TPC) to discover groups with similar time-to-event outcomes to support clinical utility. We applied these methods to data from 585 men on AS with longitudinal and comprehensive follow-up (median 4.4 years). Time-dependent C-indices and Brier scores were calculated and compared to Cox regression and landmarking methods. Both Cox and DDHL models including only baseline variables showed comparable C-indices but the DDHL model performance improved with additional follow-up data. With 3 years of data collection and 3 years follow-up the DDHL model had a C-index of 0.79 (±0.11) compared to 0.70 (±0.15) for landmarking Cox and 0.67 (±0.09) for baseline Cox only. Model calibration was good across all models tested. The AC-TPC method further discovered 4 distinct outcome-related temporal clusters with distinct progression trajectories. Those in the lowest risk cluster had negligible progression risk while those in the highest cluster had a 50% risk of progression by 5 years. In summary, we report a novel machine learning approach to inform personalised follow-up during active surveillance which improves predictive power with increasing data input over time.