Objectives: Risk calculators (RCs) improve patient selection for prostate biopsy with clinical/demographic information, recently with prostate MRI using the prostate imaging reporting and data system (PI-RADS). Fully-automated deep learning (DL) analyzes MRI data independently, and has been shown to be on par with clinical radiologists, but has yet to be incorporated into RCs. The goal of this study is to re-assess the diagnostic quality of RCs, the impact of replacing PI-RADS with DL predictions, and potential performance gains by adding DL besides PI-RADS., Material and Methods: One thousand six hundred twenty-seven consecutive examinations from 2014 to 2021 were included in this retrospective single-center study, including 517 exams withheld for RC testing. Board-certified radiologists assessed PI-RADS during clinical routine, then systematic and MRI/Ultrasound-fusion biopsies provided histopathological ground truth for significant prostate cancer (sPC). nnUNet-based DL ensembles were trained on biparametric MRI predicting the presence of sPC lesions (UNet-probability) and a PI-RADS-analogous five-point scale (UNet-Likert). Previously published RCs were validated as is; with PI-RADS substituted by UNet-Likert (UNet-Likert-substituted RC); and with both UNet-probability and PI-RADS (UNet-probability-extended RC). Together with a newly fitted RC using clinical data, PI-RADS and UNet-probability, existing RCs were compared by receiver-operating characteristics, calibration, and decision-curve analysis., Results: Diagnostic performance remained stable for UNet-Likert-substituted RCs. DL contained complementary diagnostic information to PI-RADS. The newly-fitted RC spared 49% [252/517] of biopsies while maintaining the negative predictive value (94%), compared to PI-RADS ≥ 4 cut-off which spared 37% [190/517] (p < 0.001)., Conclusions: Incorporating DL as an independent diagnostic marker for RCs can improve patient stratification before biopsy, as there is complementary information in DL features and clinical PI-RADS assessment., Clinical Relevance Statement: For patients with positive prostate screening results, a comprehensive diagnostic workup, including prostate MRI, DL analysis, and individual classification using nomograms can identify patients with minimal prostate cancer risk, as they benefit less from the more invasive biopsy procedure., Key Points: The current MRI-based nomograms result in many negative prostate biopsies. The addition of DL to nomograms with clinical data and PI-RADS improves patient stratification before biopsy. Fully automatic DL can be substituted for PI-RADS without sacrificing the quality of nomogram predictions. Prostate nomograms show cancer detection ability comparable to previous validation studies while being suitable for the addition of DL analysis., Competing Interests: Compliance with ethical standards Guarantor The scientific guarantor of this publication is David Bonekamp. Conflict of interest Albrecht Stenzinger reports speakers honoraria for Aignostics, Amgen, Astra Zeneca, AGCT, Bayer, Bristol-Myers Squibb, Eli Lilly, Illumina, Incyte, Janssen, MSD, Novartis, Qlucore, Pfizer, Roche, Seagen, Seattle Genetics, Takeda, Thermo Fisher and grants from Bayer, Bristol-Myers Squibb, Chugai, and Incyte. Heinz-Peter Schlemmer declares consulting fees or honoraria from Bayer, Bracco; travel support from Siemens, Bayer, Bracco; consultancy for Bayer; grants/grants pending from EU, BMBF, Deutsche Krebshilfe; payment for lectures from Bayer, Bracco. Heinz-Peter Schlemmer is member of the Advisory Editorial Board of European Radiology. He has not taken part in the review or selection process of this article. David Bonekamp received lecture payments from Bayer Vital. Heinz-Peter Schlemmer is a member of the European Radiology Editorial Board. He has not taken part in the review or selection process of this article. The remaining authors declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry Thomas Hielscher, a co-author of this study, is a biostatistician at the German Cancer Research Center (DKFZ), Heidelberg, Germany, and contributed to the statistical analysis for this paper. Informed consent Written informed consent was waived by the Institutional Review Board (S-164/2019) in Heidelberg. Ethical approval Institutional Review Board approval was obtained with ethics review in Heidelberg (S-164/2019). Study subjects or cohorts overlap One thousand six hundred ten out of the 1627 MRI examinations included in this study have been previously reported. The previous publications focused on DL and radiomics [19, 20, 39], however, data have not been used for systematic clinical RC assessment or development. Regarding the PI-RADS/PSAD biopsy strategy, the test set of a previous study overlaps with 101 exams from biopsy-naïve patients with PI-RADS 3 lesions in the current study [33]. Methodology RetrospectiveDiagnostic and prognostic studyPerformed at one institution, (© 2024. The Author(s).)