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Introduction: Immunotherapy is effective in a small percentage of patients with cancer and no reliable predictive biomarkers are currently available. Artificial Intelligence algorithms may automatically quantify radiologic characteristics associated with disease response to medical treatments., Methods: We investigated an innovative approach based on a 3-dimensional (3D) deep radiomics pipeline to classify visual features of chest-abdomen computed tomography (CT) scans with the aim of distinguishing disease control from progressive disease to immune checkpoint inhibitors (ICIs). Forty-two consecutive patients with metastatic urothelial cancer had progressed on first-line platinum-based chemotherapy and had baseline CT scans at immunotherapy initiation. The 3D-pipeline included self-learned visual features and a deep self-attention mechanism. According to the outcome to the ICIs, a 3D deep classifier semiautomatically categorized the most discriminative region of interest on the CT scans., Results: With a median follow-up of 13.3 months (95% CI, 11.1-15.6), the median overall survival was 8.5 months (95% CI, 3.1-13.8). According to disease response to immunotherapy, the median overall survival was 3.6 months (95% CI, 2.0-5.2) for patients with progressive disease; it was not yet reached for those with disease control. The predictive accuracy of the 3D-pipeline was 82.5% (sensitivity 96%; specificity, 60%). The addition of baseline clinical factors increased the accuracy to 92.5% by improving specificity to 87%; the accuracy of other architectures ranged from 72.5% to 90%., Conclusion: Artificial Intelligence by 3D deep radiomics is a potential noninvasive biomarker for the prediction of disease control to ICIs in metastatic urothelial cancer and deserves validation in larger series., (Copyright © 2021 Elsevier Inc. All rights reserved.)