Liquid-based genomic profiling in high-risk localized prostate cancer

Background: Tumor genomic profiling using liquid biopsies offers a minimally invasive alternative to tissue biopsy-based approach, with advantages in accessibility, tumor heterogeneity representation, and repeatability. While established in metastatic prostate cancer, its feasibility in localized disease remains unclear due to low ctDNA levels. Methods: We evaluated the feasibility and performance of tissue and liquid-based genomic profiling in patients with high-risk localized prostate cancer enrolled in a phase 2 neoadjuvant trial. Genomic DNA from formalin-fixed paraffin-embedded (FFPE) tissue and cell-free DNA from plasma were analyzed using Illumina TruSight Oncology 500 panels and DRAGEN™ pipelines, with in-house filtering of artifacts and germline variants. Results: = 4). Conclusions: Liquid-based genomic profiling is feasible and achieved high sequencing success rates in high-risk localized prostate cancer. Although concordance analysis was limited, plasma-based profiling showed robust sequencing performance and detected biologically relevant alterations. These findings support liquid biopsy as a complementary approach for molecular characterization, particularly when tissue samples are limited or of suboptimal quality. Larger studies are required to establish concordance and clinical utility.