It is not rare to experience a biochemical recurrence (BCR) following radical prostatectomy (RP) for prostate cancer (PCa). It has been reported that early detection and management of BCR following surgery could improve survival in PCa. This study aimed to develop a nomogram integrating deep learning-based radiomic features and clinical parameters to predict 1-year BCR after RP and to examine the associations between radiomic scores and the tumor microenvironment (TME).In this retrospective multicenter study, two independent cohorts of patients (n = 349) who underwent RP after multiparametric magnetic resonance imaging (mpMRI) between January 2015 and January 2022 were included in the analysis. Single-cell RNA sequencing data from four prospectively enrolled participants were used to investigate the radiomic score-related TME. The 3D U-Net was trained and optimized for prostate cancer segmentation using diffusion-weighted imaging, and radiomic features of the target lesion were extracted. Predictive nomograms were developed via multivariate Cox proportional hazard regression analysis. The nomograms were assessed for discrimination, calibration, and clinical usefulness.In the development cohort, the clinical-radiomic nomogram had an AUC of 0.892 (95% confidence interval: 0.783--0.939), which was considerably greater than those of the radiomic signature and clinical model. The Hosmer-Lemeshow test demonstrated that the clinical-radiomic model performed well in both the development (P = 0.461) and validation (P = 0.722) cohorts.Decision curve analysis revealed that the clinical-radiomic nomogram displayed better clinical predictive usefulness than the clinical or radiomic signature alone in both cohorts. Radiomic scores were associated with a significant difference in the TME pattern.Our study demonstrated the feasibility of a DWI-based clinical-radiomic nomogram combined with deep learning for the prediction of 1-year BCR. The findings revealed that the radiomic score was associated with a distinctive tumor microenvironment.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.