AI-based lung cancer screening is constrained by scarce, annotated CT data, particularly for rare nodule presentations. We investigate whether physics-based, anatomy-informed simulated CT can improve AI performance across three lung-nodule tasks: detection, segmentation, and malignancy classification. Using the Virtual Lung Screening Trial framework, we generated 174 digital human twins (XCAT3), embedded 512 procedurally controlled nodules (X-Lesions, 4-30 mm), and simulated CT (DukeSim) under two scanner configurations, yielding 1,044 annotated scans. Combined with clinical data, these trained models for detection (MONAI), segmentation (VISTA3D, nnU-Net), and classification (Med3D), evaluated on external test sets. Detection sensitivity at 1 FP/scan rose from 0.37 to 0.56 (p < 0.001); segmentation improved modestly (Dice 0.61 to 0.64, 0.66 to 0.69); classification AUC rose from 0.78 to 0.87 (p < 0.001). Physics-based virtual imaging trials can help address data scarcity in medical AI.

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