Deriving interpretable prognostic features from deep-learning-based prognostic histopathology models remains a challenge. In this study, we developed a deep learning system (DLS) for predicting disease specific survival for stage II and III colorectal cancer using 3,652 cases (27,300 slides). When evaluated on two validation datasets containing 1,239 cases (9,340 slides) and 738 cases (7,140 slides) respectively, the DLS achieved a 5-year disease-specific survival AUC of 0.70 (95%CI 0.66-0.73) and 0.69 (95%CI 0.64-0.72), and added significant predictive value to a set of 9 clinicopathologic features. To interpret the DLS, we explored the ability of different human-interpretable features to explain the variance in DLS scores. We observed that clinicopathologic features such as T-category, N-category, and grade explained a small fraction of the variance in DLS scores (R2=18% in both validation sets). Next, we generated human-interpretable histologic features by clustering embeddings from a deep-learning based image-similarity model and showed that they explain the majority of the variance (R2 of 73% to 80%). Furthermore, the clustering-derived feature most strongly associated with high DLS scores was also highly prognostic in isolation. With a distinct visual appearance (poorly differentiated tumor cell clusters adjacent to adipose tissue), this feature was identified by annotators with 87.0-95.5% accuracy. Our approach can be used to explain predictions from a prognostic deep learning model and uncover potentially-novel prognostic features that can be reliably identified by people for future validation studies.

本研究通过开发基于深度学习的系统，在3,652例（27,300张切片）的结直肠癌患者中进行预测，探索人类可解释的患病特征并阐述其潜在预测价值。通过对两个验证数据集分别包含1,239例（9,340张切片）和738例（7,140张切片）的评估，该系统实现了0.70和0.69的5年疾病特异性存活AUC，并为一组9个临床病理特征提供了显著的预测价值。

基于深度学习的结直肠癌可解释性生存预测