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

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Liquid biopsies offer a less invasive method for tumor genomic profiling compared to tissue biopsies.
• Challenges exist in applying liquid biopsies to localized prostate cancer due to low circulating tumor DNA (ctDNA) levels.

Purpose of the Study:

• To assess the feasibility and performance of both tissue and liquid-based genomic profiling in patients with high-risk localized prostate cancer.
• To compare the effectiveness of plasma-based ctDNA analysis versus traditional tissue biopsy for molecular characterization.

Main Methods:

• Patients with high-risk localized prostate cancer underwent genomic profiling using formalin-fixed paraffin-embedded (FFPE) tissue and plasma ctDNA.
• Analysis employed Illumina TruSight Oncology 500 panels and DRAGEN™ pipelines, with specific filtering for artifacts and germline variants.

Main Results:

• Tissue biopsy success rate was 54.5% (12/22) due to DNA quality/quantity issues.
• Plasma samples (27/27, 100%) were successfully sequenced, demonstrating high feasibility despite low ctDNA.
• Both methods detected an average of 3.5 genomic variants, with liquid profiling offering superior coverage and depth for low-frequency mutations.

Conclusions:

• Liquid-based genomic profiling is feasible and successful in high-risk localized prostate cancer.
• Plasma profiling demonstrates robust performance and detects relevant alterations, supporting its use when tissue is limited.
• Further research is needed to confirm concordance and clinical utility in larger cohorts.