Ozone Therapy Shows Improvement in Prostate Molecular Health: A Pilot Evaluation Using the EpiSwitch Prostate Cancer Detection (PSE) Test

Abstract Prostate cancer (PCa) screening relies primarily on serum prostate-specific antigen (PSA), though its limited specificity often leads to unnecessary biopsies. The EpiSwitch® Prostate Cancer Detection (PSE) Test is a validated, 94%-accurate, blood-based assay that measures 3D genomic conformations associated with clinically significant PCa. It has demonstrated utility in reducing biopsy frequency while maintaining high diagnostic sensitivity, providing a complementary molecular tool for prostate disease assessment. Ozone therapy has been proposed as an adjunct intervention with immunomodulatory and anti-inflammatory properties, but its molecular and epigenomic effects within the prostate remain poorly defined. Ten men (ages 54–76) underwent baseline PSA and PSE testing prior to intraprostatic ozone administration (20 μg/mL; 40 mL), followed by repeat testing 30 days post-treatment. Mean PSA decreased by 20%, while mean PSE probability scores declined 31% (p = 0.045). Eight of ten participants (80%) exhibited a measurable decrease in molecular risk for clinically significant prostate cancer based on PSE profiling, including two who converted from high to low PSE classification. Multivariate analyses demonstrated consistent directional changes and distinct post-treatment clustering of epigenomic profiles, indicating coordinated modulation of chromatin signatures linked to PCa biology. These preliminary findings suggest that intraprostatic ozone therapy may favorably recalibrate prostate-associated epigenomic states, supporting further evaluation in larger, longitudinal studies.