Success of Liquid Tumor Biopsy in Men with Metastatic Prostate Cancer According to Self-Identified Race.

Abstract

Liquid biopsy using cell-free DNA (cfDNA) is increasingly used to identify somatic prostate cancer (PrCa) alterations when tissue biopsy of a metastatic lesion is infeasible or impractical. High-risk somatic alterations identified by cfDNA have been recently shown to predict the benefit of metastasis-directed therapy with stereotactic body radiation therapy in PrCa. However, given the older age of PrCa patients, liquid biopsy is often contaminated with alterations related to clonal hematopoiesis of indeterminate potential (CHIP), generating uncertainty in the clinical utility of the results. Given the higher incidence and aggressiveness of metastatic PrCa in Black men, we sought to determine if the success of cfDNA testing varied by race in a large and diverse cohort of United States Veterans with metastatic PrCa, hypothesizing that race would not influence the success of cfDNA testing. Veterans with metastatic PrCa underwent next-generation sequencing of cfDNA biopsy specimens through the VA National Precision Oncology Program from February 2019 to November 2022. Successful identification of PrCa with cfDNA testing was defined as the identification of an alteration in one or more PrCa-related related genes in the gene panel tested (AR, CDK12, SPOP, MED12, CCND1, BRAF, AKT1, TMPRSS2, ERG, ETV1, and ETV4). Univariate logistic regression was employed to explore the association between patient self-identified race, as well as other patient and disease-specific factors at the time of cfDNA biopsy, with the likelihood of yielding a successful cfDNA biopsy result. A total of 2066 cfDNA tests from 1985 Veterans were related to a diagnosis of PrCa, passed quality control measures, and were linkable to patient-level demographics. Median age at testing was 74, median PSA at testing was 22.7, median PSA doubling time (PSADT) was 3.6 months, and median Gleason score was 8. 57% of Veterans self-identified as White, 33% as Black, and 10% as Other. Eight hundred fourteen (39%) tests were deemed successful by finding a PrCa related gene alteration. Among successful tests, the most frequently encountered alterations were AR alterations in 60.4% White men and 33.9% Black men (p = 0.72), followed by TMPRSS2 alterations in 70.3% White men and 22.0% Black men (p<0.001). Despite a lower rate of PrCa-specific alterations in Black men, on univariate analysis, Veteran self-identified race was not associated with successful cfDNA testing (OR 0.95, 95% CI 0.78-1.14, p = 0.6), whereas PSA in quintiles 2-4, PSADT <12 months, and unit increase in Gleason score were associated with successful cfDNA testing (p<0.01 for all). Successful cfDNA biopsy in metastatic PrCa is associated with PSA and PSADT, but not related to patient self-identified race. In appropriate clinical scenarios, patients who self-identify as Black or White are equally likely to have PrCa-specific alterations detected on cfDNA testing when evaluating metastatic PrCa patients for local and systemic therapies.