Objectives To create a radiomics approach based on multiparametric magnetic resonance imaging (mpMRI) features extracted from an auto-fixed volume of interest (VOI) that quantifies the phenotype of clinically significant (CS) peripheral zone (PZ) prostate cancer (PCa). Methods This study included 206 patients with 262 prospectively called mpMRI prostate imaging reporting and data system 3-5 PZ lesions. Gleason scores > 6 were defined as CS PCa. Features were extracted with an auto-fixed 12-mm spherical VOI placed around a pin point in each lesion. The value of dynamic contrast-enhanced imaging(DCE), multivariate feature selection and extreme gradient boosting (XGB) vs. univariate feature selection and random forest (RF), expert-based feature pre-selection, and the addition of image filters was investigated using the training (171 lesions) and test (91 lesions) datasets. Results The best model with features from T2-weighted (T2-w) + diffusion-weighted imaging (DWI) + DCE had an area under the curve (AUC) of 0.870 (95% CI 0.980-0.754). Removal of DCE features decreased AUC to 0.816 (95% CI 0.920-0.710), although not significantly (p = 0.119). Multivariate and XGB outperformed univariate and RF (p = 0.028). Expert-based feature pre-selection and image filters had no significant contribution. Conclusions The phenotype of CS PZ PCa lesions can be quantified using a radiomics approach based on features extracted from T2-w + DWI using an auto-fixed VOI. Although DCE features improve diagnostic performance, this is not statistically significant. Multivariate feature selection and XGB should be preferred over univariate feature selection and RF. The developed model may be a valuable addition to traditional visual assessment in diagnosing CS PZ PCa.