Saliva-Based Polygenic Risk Scores and AI-Enhanced Imaging for Prostate Cancer Screening Beyond PSA

Background Prostate-specific antigen (PSA) testing, long used for prostate cancer screening, is limited by poor specificity (~25%), leading to unnecessary biopsies in over 70% of cases and substantial healthcare costs. Methods This review synthesizes recent evidence (2023–2025) on emerging non-invasive diagnostics—saliva-based polygenic risk scores (PRS) and artificial intelligence (AI) -enhanced imaging—as potential alternatives to PSA. Results Saliva-derived PRS, incorporating over 130 genetic variants, have demonstrated superior risk stratification. In the BARCODE1 trial, 40% of men with high PRS proceeded to targeted MRI and biopsy, detecting aggressive cancer in 55. 1% of cases—outperforming PSA-based detection. Concurrently, AI-assisted multiparametric MRI (mpMRI) has shown diagnostic accuracies up to 92% for clinically significant tumors (Gleason ≥7), while reducing radiologist workload by approximately 50%. Combining PRS and AI, as explored in multi-modal strategies (e. g. , PATHFINDER trial), has yielded sensitivity rates up to 95% and demonstrated cost-effectiveness, with projected savings of ~50, 000 per quality-adjusted life year. Conclusion However, disparities persist: PRS performance varies by ancestry, and AI models trained on homogeneous datasets show reduced accuracy in underrepresented populations, as highlighted in the TRANSFORM trial.