Simple SummaryThe detection of specific genomic alterations is growing in importance for therapeutic decision-making in advanced prostate cancer. Traditional methods using tumor tissue samples can be challenging for prostate cancer, as the disease is often characterized by an extended disease history and a propensity for metastasis to the bone. Given the circumstances, liquid biopsy can be an attractive alternative. In this study, we evaluated the clinical usefulness of a liquid biopsy using blood samples instead of tumor tissues. The results showed that the liquid biopsy was able to evaluate cancer-related genomic changes in most patients, and it successfully detected clinically important mutations, exhibiting the high sensitivity of liquid biopsy compared to the tissue sequencing results. The liquid biopsy also enabled a genomic evaluation in cases where it would have been not possible using only archived tumor tissue samples. This study suggests that a liquid biopsy can be a good option for checking gene changes in advanced prostate cancer patients.AbstractTraditional tissue-based assessments of genomic alterations in castration-resistant prostate cancer (CRPC) can be challenging. To evaluate the real-world clinical utility of liquid biopsies for the evaluation of genomic alterations in CRPC, we preemptively collected available plasma samples and archival tissue samples from patients that were being treated for clinically confirmed CRPC. The cell-free DNA (cfDNA) and tumor tissue DNA were analyzed using the AlphaLiquid®100-HRR panel. Plasma samples from a total of 87 patients were included in this study. Somatic mutations from cfDNA were detected in 78 (89.7%) patients, regardless of the presence of overt metastasis or concomitant treatment given at the time of plasma sample collection. Twenty-three patients were found to have known deleterious somatic or germline mutations in HRR genes from their cfDNA. Archival tissue samples from 33 (37.9%) patients were available for comparative analysis. Tissue sequencing was able to yield an NGS result in only 51.5% of the tissue samples. The general sensitivity of cfDNA for detecting somatic mutations in tissues was 71.8%, but important somatic/germline mutations in HRR genes were found to have a higher concordance (100%). Liquid biopsies can be a reasonable substitute for tissue biopsies in CRPC patients when evaluating genomic alterations.