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.
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.
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.
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.
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.
European urology focus. 2024 Mar 15 [Epub ahead of print]
Philipp Mandel, Benedikt Hoeh, Clara Humke, Claudia Doering, Mike Wenzel, Cristina Cano Garcia, Nina Fuhr, Florestan Koll, Anne Fassl, Derya Tilki, Thomas Steuber, Iris Faull, Jan Jeroch, Silvana Ebner, Christina Schmitt, Henning Reis, Jens Köllermann, Konstantinos D Kokkaliaris, Melanie C Demes, Felix K H Chun, Peter J Wild
Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany. Electronic address: ., Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany., Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Koc University Hospital, Istanbul, Turkey., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Guardant Health, Palo Alto, CA, USA., Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt am Main, Germany; German Cancer Consortium, Frankfurt/Mainz Partner Site, Frankfurt am Main, Germany., Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany; Frankfurt Institute for Advanced Studies (FIAS), Frankfurt am Main, Germany.