Prevalence of homologous recombination repair deficiencies in prostate cancer in the Russian Federation.

Abstract

e17062 Background: Homologous recombination repair (HRR) deficiency represents a frequent and clinically significant molecular event in prostate cancer (PC). The reported prevalence of HRR pathway alterations in metastatic prostate cancer (mPC) cohorts from international studies ranges from 15% to 33%, with germline variants accounting for a considerable subset of these alterations. The observed frequency, however, is not uniform globally; it is influenced by regional disparities in diagnostic accessibility and different clinical guidelines. HRR pathway alterations are associated with more aggressive disease and significantly influence both prognosis and sensitivity to PARP inhibitors and platinum-based therapies. The aim of the research was exploration of the spectrum and frequency of somatic and germline mutations in patients with PC within the Russian population. Methods: 6,447 patients with histologically confirmed PC were tested for germline and somatic variants in HRR-related genes as the part of national genetic testing program launched by the Russian Society of Clinical Oncology (RUSSCO)— “Improving Molecular-Genetic Diagnostics in the Russian Federation (2020–2025)”. 93.2% from them were mPC. 5 050 FFPE tumor samples (78,3%) and 1397 whole blood samples (21,7%) were successfully tested using next generation sequencing assays (Atlas Solo-test HRR panel (2,858 – 44.33%), AmoyDx HANDLE HRR NGS Panel, 24 (1,083 – 16.8%), Atlas Solo-test АВС panel (54 – 2.39%), laboratory-developed test (2,352 – 36.49%). Results: We identified 899 alterations in FFPE samples (17,8%) and 132 in whole blood samples (9,4%). In 19 FFPE samples we detected more than one aberration. A list of altered HRR genes in tested HRR related genes is presented in table. Conclusions: This dataset represents the largest registry of HRR alterations in mPC in the Russian Federation to date. Expanding access to genetic testing offers a valuable opportunity to personalize treatment strategies for mPC. Thus, this population-specific data analysis enables the stratification of patients based on their predicted sensitivity to targeted therapies, which may meaningfully improve their clinical prognosis. A list of altered HRR genes. Genetic alteration FFPE tumor samples/№ FFPE tumor samples/% Whole blood samples/№ Whole blood samples/% ATM 225 25.0 17 12.9 BRCA1 100 11.1 3 2.3 BRCA2 222 24.7 43 32.6 BRIP1 24 2.7 1 0.8 CDK12 91 10.1 0 0 CHEK2 114 12.7 57 43.2 PALB2 44 4.9 6 4.5 RAD51B/C/D 26 2.9 0 0 Other alterations 53 5.9 5 3.8 Total 899 132