Genomic diversity between primary tumor tissue and tumor circulating cell-free DNA (cfDNA) in patients (pts) with metastatic prostate cancer.

Abstract

189 Background: Tumor tissue and tumor cfDNA next-generation sequencing (NGS) tests are obtained in pts with metastatic prostate cancer and have demonstrated a diverse genomic landscape. High-level evidence does not exist for utilizing these tests to guide treatment selection in these pts. Targeted therapies are available for metastatic prostate cancer treatment and clinical trials are investigating drugs targeting specific molecular pathways. The objective of this study was to assess type and number of genomic aberrations between tumor tissue and cfDNA. Methods: Pts with metastatic prostate cancer who had both tissue and cfDNA results were selected and genomic profiles were compared between these two technologies. The mean number of tissue mutations was compared to cfDNA mutations for all pts using the t-test. The mutations for both tests were then categorized into five pathways: DNA repair, cell cycle regulation, PI3K, epigenetics, and androgen receptor (AR). For each pathway, the total number of patients with a mutation was compared between tissue and cfDNA using the Mann-Whitney test. Results: Nineteen pts were identified with both tissue and cfDNA results. The mean number of mutations identified was significantly less with cfDNA (95% CI, 2.7-5.3) compared to tissue (95% CI, 7.0-9.7; P < 0.0001). There were significantly more patients with PI3K pathway mutations identified in the tissue compared to cfDNA (73.7% vs 21.1% P = 0.0018), as well as epigenetic mutations (47.4% vs 0.0% P = 0.0012). There was no difference in the number of patients identified to have DNA repair, cell cycle regulation, and AR variances between the two tests. Conclusions: The lower number of aberrations detected by the cfDNA test may have occurred due to lower sensitivity of cfDNA compared to tissue based NGS. Discordance in the type of genomic variances between the two tests suggests intra-individual genetic diversity, and these results may have implications in treatment selection of pts with metastatic prostate cancer. Data are hypothesis generating and need further investigation in a larger cohort.