Germline mutations in patients with metastatic prostate cancer: A prospective cohort study in South Korea (KCSG GU20-19).

Background: Several clinical guidelines recommend screening for hereditary prostate cancer in high-risk groups for metastatic prostate cancer. However, despite the recent increase in the diagnosis of prostate cancer in Korea, genetic testing for hereditary prostate cancer is not being performed, making it impossible to know the frequency of hereditary prostate cancer. This study aimed to determine the prevalence of germline mutations in unselected Korean patients with metastatic prostate cancer. Methods: Between July 2021 and December 2022, metastatic prostate cancer patients were enrolled prospectively, without any specific selection based on age or family history. Germline mutation analysis was performed on DNA from blood via next generation sequencing using SOLIDaccuTestTM DNA HRD (NgeneBio, Korea). Results: A total of 301 patients were enrolled and the prevalence of germline mutation was analyzed. At diagnosis, the median age was 67 (46-91 years old), and the median PSA was 150 ng/mL (3.07-5000). 250 patients had a Gleason score of 8 or higher. 36 patients (12.0 %) carried a pathogenic (14/301, 4.6 %)/likely pathogenic (22/301, 7.3 %) variant in a germline mutation. Of these patients, 11 patients (3.65 %) had BRCA2 mutations. ATM (6/301, 1.99 %) was the second most frequently mutated gene, followed by FH (4/301, 1.33 %), FANCA, FANCD2, MRE11, SLFN11, SMO (0.66 % of each, 2/301), BLM, CHEK2, ERBB3, MAP2K1, and VHL (0.33 % of each, 1/301). Further analysis will be conducted to evaluate the impact of germline mutations on somatic mutation results, treatment patterns, and clinical outcomes. Conclusions: The prevalence of pathogenic germline mutations among unselected Korean patients with metastatic prostate cancer was 12.0 %. Germline mutation prevalence in this cohort was comparable to previous reported results. This study provides the framework for the development of preventive and treatment strategies based on hereditary genetic factors for prostate cancer in the Korean population.