Peripheral and Selective Venous Liquid Biopsy Profiling in Localized Prostate Cancer: A Pilot Feasibility Study

Background Liquid biopsy profiling via next-generation sequencing (NGS) is increasingly being used in prostate cancer to identify actionable genomic alterations, monitor disease dynamics, and provide prognostic information. However, the circulating tumor DNA (ctDNA) fraction correlates with disease burden, often remaining near the analytical limit of detection in localized disease. Accordingly, strategies to enhance the molecular characterization in earlier-stage disease represent a clinically relevant priority. Methods We conducted a retrospective, single-center observational analysis in a cohort of patients with localized prostate cancer undergoing liquid biopsy. Patients underwent peripheral venous sampling for genomic profiling. When peripheral testing failed to identify genomic alterations or was non-informative, patients proceeded to selective venous blood sampling within the cavo-iliac venous compartment. The primary outcome was the detection rate of reportable genomic alterations in peripheral blood, while exploratory outcomes included findings from selective sampling. Results Thirty-one patients were enrolled. Peripheral blood liquid biopsy was evaluable in 28 patients. Genomic alterations were detected in 20 of them (20/28, 71.4%; 95% CI, 51.3–86.8%). Patients most frequently harbored mutations in ATM (21.4%), RB1 (14.3%), and BRCA1 or BRCA2 (7.1% each). Eight patients underwent selective venous sampling, with 4 out of 8 (50.0%) demonstrating the presence of at least one genomic alteration. Conversion to mutation-positive occurred in two patients (50.0%) who initially lacked detectable alterations in peripheral blood sampling. Across all available peripheral and selective samples, at least one reportable genomic alteration was identified in 23 of the 31 enrolled patients (74.2%). Conclusions Our findings demonstrate a high prevalence of genomic mutations in localized prostate cancer. Selective venous sampling was feasible and safe in this small exploratory cohort and provided additional molecular findings in selected patients. These hypothesis-generating data support selective sampling as a potential complementary approach for molecular profiling in localized prostate cancer, deserving prospective validation.