Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wenzel, M; Hoeh, B; Koll, F; Humke, C; Fassl, A; Reis, H; Wild, P; Steuber, T; Graefen, M; Tilki, D; Traumann, M; Banek, S; Chun, FKH; Mandel, P.
Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer.
BJU Int. 2025; 135(1): 117-124.
Doi: 10.1111/bju.16462
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- Co-Autor*innen der Med Uni Graz
- Koll Florestan Johannes
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- Abstract:
- OBJECTIVE: To investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP-ribose)-polymerase (PARPi) as systemic therapy for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Of all HRR-screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan-Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS. RESULTS: Of 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia-telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin-dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR-positive vs -negative patients. Specifically in hormone-sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03). CONCLUSION: Incidence of HRR alteration in a clinical real-world setting is high when using blood- and tissue-based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA-positive patients with mCRPC with and without PARPi usage vs HRR/BRCA-negative patients.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Male - administration & dosage
- Aged - administration & dosage
- Recombinational DNA Repair - genetics
- Middle Aged - administration & dosage
- Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use
- Prostatic Neoplasms, Castration-Resistant - genetics, pathology, drug therapy, mortality
- BRCA1 Protein - genetics
- BRCA2 Protein - genetics
- Cyclin-Dependent Kinases - genetics
- Ataxia Telangiectasia Mutated Proteins - genetics
- Genes, BRCA1 - administration & dosage
- Mutation - administration & dosage
- Genes, BRCA2 - administration & dosage
- Aged, 80 and over - administration & dosage
- Prostatic Neoplasms - genetics, pathology, mortality, drug therapy
- Checkpoint Kinase 2 - administration & dosage
- Find related publications in this database (Keywords)
- metastatic prostate cancer
- mutation
- metastatic hormone-sensitive prostate cancer
- BReast CAncer (BRCA) gene