Homologous Recombination Repair (HRR) Mutation Concordance Between Liquid Biopsy (LB) and Tumor Tissue by NGS in a Real-World Prostate Cancer (PC) Database

ASCO Genitourinary Cancers Symposium 2023 PRESENTATION
Authors John Shen, Liang Wang, Ali Raza Khaki, Rafael E Jimenez, Elizabeth Mauer, Melissa Conrad Stoppler, Calvin Y. Chao, Manish Kohli

Background:NGS to identify HRR mutations (mut) is indicated in advanced prostate cancer (aPC); samples for testing may be tissue or plasma. In a large real-world (RW) database, we determined concordance between plasma ctDNA and primary tumor tissue (PT) and/or metastatic tissue (MT) for BRCA1, BRCA2, and ATM mut in PC patients (pts) who received both LB and tissue NGS any time during standard of care (SOC) management. The study objective was to assess the utility of LB to detect actionable mut in these HRR genes and demonstrate the utility of combined LB and tissue testing.

Methods:We examined de-identified data from pts who had NGS using both Tempus xF (105 genes-LB) and Tempus xT (648 genes-tissue) during SOC for aPC. Analyses included 1) PT and LB and 2) MT and LB. The results from the pts’ earliest PT or MT and earliest LB were used for paired analyses. The prevalence of a pathogenic/likely pathogenic germline and/or somatic mut in BRCA1, BRCA2, or ATM was reported as N (%), 95% CI. The sensitivity of the LB to identify observed HRR mut in tissue was also reported as N (%), 95% CI. Concordance between pairs was evaluated by Cohen’s kappa statistic with 95% CI.

Results:HRR results are show for 1074 PC pts who had NGS performed on PT and LB and 451 PC pts with NGS on both MT and LB. In the PT and LB analysis, HRR mut were found in 6.2% (95% CI: 4.9%-7.9%) of LB and 8.8% (95% CI: 7.2%-11%) of PT. The sensitivity of LB to detect HRR mut in the PT was 53% (95% CI: 43%-64%). Cohen’s kappa statistic was 0.59, 95% CI=0.50-0.68, between PT and LB. In the MT and LB analysis, HRR mut were found in 10% (95% CI 7.8%-14%) of LB and 10% (7.6%-13%) of MT. The sensitivity of LB to detect HRR mut in the MT was 70% (95% CI: 54%-82%). Cohen’s kappa statistic was 0.65, 95% CI=0.54-0.77, between MT and LB.

Conclusions:In this large RW dataset, plasma ctDNA-based analysis of BRCA1, BRCA2, and ATM mut showed greater concordance between LB and MT than LB and PT, and may be used as an initial tool for HRR mut detection. When LB results are negative, further exploration with tissue-based testing may identify HRR mut to guide clinical decisions.

PT vs LB
MT vs LB
PT, HRR + PT, HRR – Total MT, HRR + MT, HRR – Total
LB, HRR + 50 (4.7%) 17 (1.6%) 67 (6.2%) 32 (7.1%) 15 (3.3%) 47 (10%)
LB, HRR – 44 (4.1%) 963 (90%) 1007 (94%) 14 (3.1%) 390 (86%) 404 (90%)
Total 94 (8.8%) 980 (91%) 1074 (100%) 46 (10%) 405 (90%) 451 (100%)