Article
Feasibility and comparison of liquid biopsy (ctDNA) and tumor tissue next-generation sequencing in 50 metastatic prostate cancer patients in a real-world clinical setting
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Authors
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Benedikt Hoeh
- Klinik für Urologie, Goethe Universität Frankfurt
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C. Humke
- Klinik für Urologie, Goethe Universität Frankfurt
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N. Fuhrer
- Klinik für Urologie, Goethe Universität Frankfurt
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M. Wenzel
- Klinik für Urologie, Goethe Universität Frankfurt
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F. Koll
- Klinik für Urologie, Goethe Universität Frankfurt
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D. Tilki
- Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf
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T. Steuber
- Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf
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I. Faull
- Guardant Health Inc.
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M. Demess
- Dr. Senckenberg Institute of Pathology, Goethe Universität Frankfurt
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A. Fassl
- Dr. Senckenberg Institute of Pathology, Goethe Universität Frankfurt
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J. Köllermann
- Dr. Senckenberg Institute of Pathology, Goethe Universität Frankfurt
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K. Kokkaliaris
- Dr. Senckenberg Institute of Pathology, Goethe Universität Frankfurt
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P. Wild
- Dr. Senckenberg Institute of Pathology, Goethe Universität Frankfurt
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P. Mandel
- Klinik für Urologie, Goethe Universität Frankfurt
| Published: | June 20, 2023 |
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Outline
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Objective: With FDA (Food and Drug Administration) and EMA (European Medicines Agency) approval of the Poly (ADP-ribose) polymerase inhibitor Olaparib in metastatic castration-resistant prostate cancer (mCRPC) and ongoing trials in the hormone-sensitive prostate cancer (mHSPC) setting, detection of breast cancer gene (BRCA) 2 and 1 gene alterations has gained an important role. The aim of the current study was to investigate feasibility and comparison of liquid biopsy (circulating tumor DNA [ctDNA]) and tumor tissue next-generation sequencing (NGS) in metastatic prostate cancer (mPC) patients in a real-world clinical setting.
Materials: The study cohort consisted of 50 mPC patients with tumor tissue NGS performed for BRCA2/BRCA1 alterations and consent to perform an additional liquid-biopsy NGS, treated at a university tertiary center. For tumor tissue NGS Oncomine Comprehensive Assay Version 3 (Thermo Fisher Scientific) was performed in the majority of the cases, for liquid biopsy NGS the Guardant360 83 gene assay (Guardant Health) was used.
Results: Tumor tissue NGS (primary tumor: 30/50 [61%]) was successful in 39/50 (78%) mPC patients. Among those (n=39), BRCA2, BRCA1, BRCA2 and/or BRCA1 gene alterations were prevalent in 4/39 (10%), 4/39 (10%), 6/39 (15%) patients. In contrast, liquid biopsy NGS was successful in all 50/50 (100%) patients. Here, BRCA2, BRCA1, BRCA2 and/or BRCA1 gene alteration were prevalent in 9/50 (10%), 4/50 (8%), 11/50 (22%) patients. In subgroup analyses focusing solely on patients with successful tumor tissue NGS, BRCA2 and/or BRCA1 gene alteration was prevalent in 7/39 (18%) patients relying on liquid biopsy NGS. Specifically, liquid biopsy NGS reported BRCA2 and/or BRCA1 gene alterations in 4 patients which were negative in tumor tissue NGS, yet did not report gene alterations in 3 patients which were prevalent in tumor tissue NGS. Median time between liquid biopsy sampling and tumor tissue harboring was 132 (IQR: 94–186) weeks, which might impact the rate of concordance.
Conclusions: Relying on both liquid-biopsy and tumor tissue NGS resulted in a higher detection rate of BRCA2 and/or BRCA1 gene alterations compared to tumor tissue NGS solely (22 vs 15%). Therefore, BRCA2 and/or BRCA1 gene alterations testing should be based not only on one (currently tumor tissue) but rather on both approaches to identify all PARP-inhibitor eligible mPC patients.
