Stratification of Oligometastatic Prostate Cancer Patients by Liquid Biopsy: Clinical Insights from a Pilot Study

Abstract

We propose a pilot, prospective, translational study with the aim of identifying possible molecular markers underlying metastatic prostate cancer (PC) evolution with the use of liquid biopsy. Twenty-eight castrate sensitive, oligometastatic PC patients undergoing bone and/or nodal stereotactic body radiotherapy (SBRT) were recruited. Peripheral blood samples were collected before the commencement of SBRT, then they were processed for circulating cell free DNA (cfDNA) extraction. Deep targeted sequencing was performed using a custom gene panel. The primary endpoint was to identify differences in the molecular contribution between the oligometastatic and polymetastatic evolution of PC to same-first oligo-recurrent disease presentation. Seventy-seven mutations were detected in 25/28 cfDNA samples: ATM in 14 (50%) cases, BRCA2 11 (39%), BRCA1 6 (21%), AR 13 (46%), ETV4, and ETV6 2 (7%). SBRT failure was associated with an increased risk of harboring the BRCA1 mutation (OR 10.5) (p = 0.043). The median cfDNA concentration was 24.02 ng/mL for ATM mutation carriers vs. 40.04 ng/mL for non-carriers (p = 0.039). Real-time molecular characterization of oligometastatic PC may allow for the identification of a true oligometastatic phenotype, with a stable disease over a long time being more likely to benefit from local, curative treatments or the achievement of long-term disease control. A prospective validation of our promising findings is desirable for a better understanding of the real impact of liquid biopsy in detecting tumor aggressiveness and clonal evolution.

Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection

“…Different databases, such as dbSNPs, ClinVar, and COSMIC, were interrogated and the variant frequency in the population was considered (i.e., ExAC and 1000 Genome). A coverage at 1000× was considered as acceptable for the consistence of the results [ 30 ].…”

Progress in Oligometastatic Prostate Cancer: Emerging Imaging Innovations and Therapeutic Approaches

“…The patients carrying BRCA1 mutations exhibited treatment failure following SBRT. In the future, the real-time molecular profiling of oligometastatic PCa may facilitate the identification of a genuine oligometastatic phenotype, thereby enabling a more favorable response to localized curative therapies or the attainment of sustained disease control over an extended period [36].…”

Diagnosis of Prostate Cancer through the Multi-Ligand Binding of Prostate-Derived Extracellular Vesicles and miRNA Analysis

“…There have been a number of new serum-, urine-, and tissue-based PC biomarkers developed over the last decade [5,6]. The most advanced results have been obtained by deep sequencing of cell-free DNA (cfDNA) using custom panels that allow analysis of PC-related genes [7,8]. However, these findings still have limited clinical applications.…”