PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session Q - Pathological and Oncological Sciences 2.

BRCA1/2 Mutations in Prostate Cancer: Association with Clinicopathological Parameters and Patients’ Survival


Áron Soós1, Anita Csizmarik1, Erzsébet Rásó2, Miklós Szűcs1, Péter Nyirády1, Tibor Szarvas1,3
1: Department of Urology, Semmelweis University, Budapest, Hungary
2: Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
3: Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK) - University Hospital Essen, Essen, Germany

Text of the abstract

Approximately 12% of metastatic prostate cancers (PC) harbour loss-of-function mutations in their BRCA1/2 genes. Patients with BRCA1/2 mutations exhibit reduced prognosis and different therapeutic sensitivity. PARP inhibitor (PARPi) therapy is now a targeted option for BRCA1/2-positive metastatic castration-resistant PC (mCRPC), while platinum chemotherapy maybe also effective in these cases. Current guidelines recommend BRCA1/2 testing for high-risk and particularly for metastatic PC.
Our aim was to provide an overview on the implementation of BRCA1/2 testing of PC patients in the Department of Urology, Semmelweis University. In addition, we assessed the association of BRCA1/2 mutations with clinical parameters, therapeutic sensitivity and survival of PC patients.
BRCA1/2 testing was performed from blood or tumor tissue using next generation sequencing (NGS) analyses as part of the clinical routine. As data collection is still ongoing, an interim statistical analysis was performed focusing on the BRCA1/2 genes using Chi2 test for paired comparisons and Kaplan-Meier survival curves with log-rank test for survival analysis.
Between 03/2019 and 01/2024 BRCA1/2 tests were requested for 107 PCa patients. Six patients had local PC, 38 patients had metastatic hormone-sensitive PC and 63 patients had CRPC at the time of analysis. NGS was performed for 94 PC patients using prostate biopsy (n=43), transurethral prostate biopsy (n=6), radical prostatectomy specimen (n=21), lymph node biopsy (n=1), bone biopsy (n=1) or blood samples (n=22), while for 13 patients samples were not suitable for analyses. Of the 94 PC patients 16 (15%) harboured BRCA1/2 mutation (BRCA1 n=6; BRCA2 n=10). Patients’ age, ISUP grade and serum PSA levels at first diagnosis showed no significant difference between the mutated and wild-type groups. Out of 16 BRCA1/2 positive patients six received PARPi and three patients carboplatin therapy. We found no difference between BRCA1/2 positive and negative men in terms of OS.
To our knowledge, this is the first evaluation of BRCA1/2 testing in PC in Hungary. BRCA1/2 analysis is requested mostly in metastatic stages and in most cases the results were incorporated into the clinical decision-making. BRCA1/2 positive PC patients showed similar clinicopathological characteristics and OS to BRCA1/2 wild-types.