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Abstract Malignancy grading of prostate cancer (PCa) is fundamental for risk stratification, patient counseling, and treatment decision-making. Deep learning has shown potential to improve the expert consensus for tumor grading, which relies on the Gleason score/grade grouping. However, the core problem of interobserver variability for the Gleason grading system remains unresolved. We developed a novel grading system for PCa and utilized artificial intelligence (AI) and multi-institutional international datasets from 2647 PCa patients treated with radical prostatectomy with a long follow-up of ≥10 years for biochemical recurrence and cancer-specific death. Through survival analyses, we evaluated the novel grading system and showed that AI could develop a tumor grading system with four risk groups independent from and superior to the current five grade groups. Moreover, AI could develop a scoring system that reflects the risk of castration resistant PCa in men who have experienced biochemical recurrence. Thus, AI has the potential to develop an effective grading system for PCa interpretable by human experts.