Next-Generation Precision Oncology in Prostate Cancer: Synergistic Liquid Biopsy, mpMRI, and AI-Guided Multi-Omics Strategies

Abstract:: Prostate Cancer (PCa) is the leading male malignancy worldwide; improving out-comes depends on early and accurate diagnosis coupled with reliable prognostication. Tra-ditional tools, PSA testing, and Gleason scoring suffer from limited specificity, inter-ob-server variability, and overdiagnosis. We review how integrating multi-omics (genomics, transcriptomics, epigenomics, proteomics, metabolomics) with advanced imaging (mpMRI, PI-RADS v2.1) and Artificial Intelligence (AI) is transforming precision management of PCa. Circulating tumor DNA (ctDNA) assays now detect tumour-specific mutations, copy-number changes, and methylation patterns with higher sensitivity than PSA, enabling non-invasive early diagnosis, longitudinal monitoring of minimal residual disease, and real-time tracking of clonal evolution under therapeutic pressure. Combined with circulating tumour cells, ctDNA guides adjuvant therapy decisions and uncovers actionable targets such as BRCA or AR-V7 variants. mpMRI fused with PI-RADS standardises lesion reporting, in-creases detection of clinically significant cancer, and reduces unnecessary biopsies; AI-driven segmentation and PI-RADS scoring further improve inter-reader agreement and risk stratification. Genomic and transcriptomic subtyping, AR-active, SPOP-mutant, neuroendo-crine, and immune-enriched subclasses, inform prognosis and therapy selection. Multi-om-ics prognostic signatures integrating mutation, expression, methylation, and immune fea-tures outperform traditional staging for predicting biochemical recurrence, metastasis, and treatment resistance. AI frameworks that fuse imaging, pathology, liquid-biopsy, and clini-cal data enable individualised surveillance or intensification strategies. Harmonisation of protocols, external validation, and equitable data diversity remain essential for clinical trans-lation. Continued interdisciplinary development of standardised, interpretable AI-multi-om-ics platforms will consolidate these advances into routine care, advancing truly personalised prostate-cancer medicine.