Abstract
BACKGROUND: The first sign of metastatic prostate cancer after radical prostatectomy is rising PSA levels in the blood, termed biochemical recurrence. The prediction of recurrence relies mainly on the morphological assessment of prostate cancer using the Gleason grading system. However, in this system, within-grade morphological patterns and subtle histopathological features are currently omitted, leaving a significant amount of prognostic potential unexplored. METHODS: To discover additional prognostic information using artificial intelligence, we trained a deep learning system to predict biochemical recurrence from tissue in H&E-stained microarray cores directly. We developed a morphological biomarker using convolutional neural networks leveraging a nested case-control study of 685 patients and validated on an independent cohort of 204 patients. We use concept-based explainability methods to interpret the learned tissue patterns. RESULTS: The biomarker provides a strong correlation with biochemical recurrence in two sets (n = 182 and n = 204) from separate institutions. Concept-based explanations provided tissue patterns interpretable by pathologists. CONCLUSIONS: These results show that the model finds predictive power in the tissue beyond the morphological ISUP grading.