Methylation Meets Fragmentomics: ctDNA in Early Prostate Cancer

Early detection of prostate cancer is challenged by low circulating tumor DNA (ctDNA) levels, limiting sensitivity. We evaluated whether combining methylation and fragmentomic features from cell-free DNA (cfDNA) improves detection. cfDNA from prostate cancer patients across disease stages and healthy controls was analyzed using a multiomics approach assessing 5mC, 5hmC, and fragmentomic features. Methylation signals reflected tumor biology but were less sensitive in localized disease, whereas fragmentomics provided more consistent discrimination across stages. Overall, fragmentomics offers a robust basis for early detection, and integrating both marker types is expected to further increase sensitivity and improve non-invasive prostate cancer diagnostics.