Radiomics-Based Early Triage of Prostate Cancer: A Multicenter Study from the CHAIMELEON Project

Prostate cancer (PCa) is the most commonly diagnosed malignancy in men worldwide. Accurate triage of patients based on tumor aggressiveness and staging is critical for selecting appropriate management pathways. While magnetic resonance imaging (MRI) has become a mainstay in PCa diagnosis, most predictive models rely on multiparametric imaging or invasive inputs, limiting generalizability in real-world clinical settings. This study aimed to develop and validate machine learning (ML) models using radiomic features extracted from T2-weighted MRI—alone and in combination with clinical variables—to predict ISUP grade (tumor aggressiveness), lymph node involvement (cN) and distant metastasis (cM). A retrospective multicenter cohort from three European sites in the Chaimeleon project was analyzed. Radiomic features were extracted from prostate zone segmentations and lesion masks, following standardized preprocessing and ComBat harmonization. Feature selection and model optimization were performed using nested cross-validation and Bayesian tuning. Hybrid models were trained using XGBoost and interpreted with SHAP values. The ISUP model achieved an AUC of 0.66, while the cN and cM models reached AUCs of 0.77 and 0.80, respectively. The best-performing models consistently combined prostate zone radiomics with clinical features such as PSA, PIRADSv2 and ISUP grade. SHAP analysis confirmed the importance of both clinical and texture-based radiomic features, with entropy and non-uniformity measures playing central roles in all tasks. Our results demonstrate the feasibility of using T2-weighted MRI and zonal radiomics for robust prediction of aggressiveness, nodal involvement and distant metastasis in PCa. This fully automated pipeline offers an interpretable, accessible and clinically translatable tool for first-line PCa triage, with potential integration into real-world diagnostic workflows.