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Feasibility of Next-generation Sequencing of Liquid Biopsy (Circulating Tumor DNA) Samples and Tumor Tissue from Patients with Metastatic Prostate Cancer in a Real-world Clinical Setting in Germany.

Feasibility of Next-generation Sequencing of Liquid Biopsy (Circulating Tumor DNA) Samples and Tumor Tissue from Patients with Metastatic Prostate Cancer in a Real-world Clinical Setting in Germany.

Authors :
Mandel P
Hoeh B
Humke C
Doering C
Wenzel M
Cano Garcia C
Fuhr N
Koll F
Fassl A
Tilki D
Steuber T
Faull I
Jeroch J
Ebner S
Schmitt C
Reis H
Köllermann J
Kokkaliaris KD
Demes MC
Chun FKH
Wild PJ
Source :
European urology focus [Eur Urol Focus] 2024 Mar; Vol. 10 (2), pp. 339-345. Date of Electronic Publication: 2024 Mar 15.
Publication Year :
2024

Abstract

Background and Objective: With European Medicines Agency approval of PARP inhibitors in metastatic castration-resistant prostate cancer and ongoing trials in metastatic hormone-sensitive prostate cancer, detection of genetic alterations in BRCA1/2 and other homologous recombination repair genes has gained an important role. Our aim was to investigate the feasibility and comparability of comprehensive next-generation sequencing (NGS) of liquid biopsy (LB; circulating tumor DNA) and tumor tissue (TT) samples in a real-world clinical setting.<br />Methods: The study cohort consisted of 50 patients with metastatic prostate cancer (mPC) who had TT NGS performed for BRCA1/2 alterations and consent for additional LB NGS. The Oncomine Comprehensive Assay v3 (Thermo Fisher Scientific, Waltham, MA, USA) was used for TT NGS. The Guardant360 83-gene assay (Guardant Health, Palo Alto, CA, USA) was used for LB NGS, including all types of somatic alterations, microsatellite instability, and blood tumor mutational burden. We calculated BRCA1/2 alteration rates and the negative percentage agreement (NPA) and positive percentage agreement (PPA) between TT and LB results.<br />Key Findings and Limitations: TT NGS was successful in 44/50 patients (88%), with pathogenic BRCA1/2 alterations detected in four (9%). LB NGS was successful in all 50 patients (100%), with BRCA1/2 alterations detected in ten (20%). In a subgroup analysis for the 44 patients with successful TT NGS, NPA was 85% and PPA was 50%. The median time between TT sample collection and blood sampling for NGS was 132 wk (IQR 94-186). The limited sample size and differences in the time of NGS assessment are limitations.<br />Conclusions and Clinical Implications: LB NGS resulted in a higher detection rate for BRCA1/2 alterations in comparison to conventional TT NGS (20% vs 9%). Ideally, BRCA1/2 testing should be based on both approaches to identify all patients with mPC eligible for PARP inhibitor therapy.<br />Patient Summary: Our study shows that genetic tests for both tumor tissue and blood samples results in higher rates of detection of BRCA1/2 gene alterations in patients with metastatic prostate cancer.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
2405-4569
Volume :
10
Issue :
2
Database :
MEDLINE
Journal :
European urology focus
Publication Type :
Academic Journal
Accession number :
38493067
Full Text :
https://doi.org/10.1016/j.euf.2024.02.007