Gleason grading of prostate cancer is an important prognostic factor but suffers from poor reproducibility, particularly among non-subspecialist pathologists. Although artificial intelligence (A.I.) tools have demonstrated Gleason grading on-par with
expert pathologists, it remains an open question whether A.I. grading translates to better prognostication. In this study, we developed a system to predict prostate-cancer specific mortality via A.I.-based Gleason grading and subsequently evaluated its ability to risk-stratify patients on an independent retrospective cohort of 2,807 prostatectomy cases from a single European center with 5-25 years of follow-up (median: 13, interquartile range 9-17). The A.I.s risk scores produced a C-index of 0.84 (95%CI 0.80-0.87) for prostate cancer-specific mortality. Upon discretizing these risk scores into risk groups analogous to pathologist Grade Groups (GG), the A.I. had a C-index of 0.82 (95%CI 0.78-0.85). On the subset of cases with a GG in the original pathology report (n=1,517), the A.I.s C-indices were 0.87 and 0.85 for continuous and discrete grading, respectively, compared to 0.79 (95%CI 0.71-0.86) for GG obtained from the reports. These represent improvements of 0.08 (95%CI 0.01-0.15) and 0.07 (95%CI 0.00-0.14) respectively. Our results suggest that A.I.-based Gleason grading can lead to effective risk-stratification and warrants further evaluation for improving disease management.
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 colorecta
l 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.
