Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as different phenotypic appearances on magnetic resonance imaging (MRI). This region surrounding the PCa lesion, or the peri-tumoral region, may encode useful information that can complement intra-tumoral information to enable better risk stratification. Purpose: To evaluate the role of peri-tumoral radiomic features on bi-parametric MRI (T2-weighted and Diffusion-weighted) to distinguish PCa risk categories as defined by D'Amico Risk Classification System. Materials and Methods: We studied a retrospective, HIPAA-compliant, 4-institution cohort of 231 PCa patients (n = 301 lesions) who underwent 3T multi-parametric MRI prior to biopsy. PCa regions of interest (ROIs) were delineated on MRI by experienced radiologists following which peri-tumoral ROIs were defined. Radiomic features were extracted within the intra- and peri-tumoral ROIs. Radiomic features differentiating low-risk from: (1) high-risk (L-vs.-H), and (2) (intermediate- and high-risk (L-vs.-I + H)) lesions were identified. Using a multi-institutional training cohort of 151 lesions (D1, N = 116 patients), machine learning classifiers were trained using peri- and intra-tumoral features individually and in combination. The remaining 150 lesions (D2, N = 115 patients) were used for independent hold-out validation and were evaluated using Receiver Operating Characteristic (ROC) analysis and compared with PI-RADS v2 scores. Results: Validation on D2 using peri-tumoral radiomics alone resulted in areas under the ROC curve (AUCs) of 0.84 and 0.73 for the L-vs.-H and L-vs.-I + H classifications, respectively. The best combination of intra- and peri-tumoral features resulted in AUCs of 0.87 and 0.75 for the L-vs.-H and L-vs.-I + H classifications, respectively. This combination improved the risk stratification results by 3-6% compared to intra-tumoral features alone. Our radiomics-based model resulted in a 53% accuracy in differentiating L-vs.-H compared to PI-RADS v2 (48%), on the validation set. Conclusion: Our findings suggest that peri-tumoral radiomic features derived from prostate bi-parametric MRI add independent predictive value to intra-tumoral radiomic features for PCa risk assessment.

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