Early detection of clinically significant prostate cancer (csPCa) has substantially improved with the latest PI-RADS versions. However, there is still an overdiagnosis of indolent lesions (iPCa), and radiomics has emerged as a potential solution. The aim of this systematic review is to evaluate the role of handcrafted and deep radiomics in differentiating lesions with csPCa from those with iPCa and benign lesions on prostate MRI assessed with PI-RADS v2 and/or 2.1. The literature search was conducted in PubMed, Cochrane, and Web of Science databases to select relevant studies. Quality assessment was carried out with Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), Radiomic Quality Score (RQS), and Checklist for Artificial Intelligence in Medical Imaging (CLAIM) tools. A total of 14 studies were deemed as relevant from 411 publications. The results highlighted a good performance of handcrafted and deep radiomics methods for csPCa detection, but without significant differences compared to radiologists (PI-RADS) in the few studies in which it was assessed. Moreover, heterogeneity and restrictions were found in the studies and quality analysis, which might induce bias. Future studies should tackle these problems to encourage clinical applicability. Prospective studies and comparison with radiologists (PI-RADS) are needed to better understand its potential.