Introduction:

There’s increasing awareness that men with prostate cancer (PC) frequently harbor germline mutations (GM) that may carry important implications for them and their family members. Most studies evaluated GM rates in men with metastatic disease and a recent publication reported an overall detection rate of 17% in both metastatic and localized PC patients. Here, we sought to compare GM rates in metastatic and localized PC patients.

Methods:

Between 2017 – 2019 men diagnosed with PC at Michigan Medicine and Michigan Institute of Urology (MIU) were offered genetic testing in accordance with NCCN guidelines. Patient data was tracked in a prospectively collected registry including multiple patient data points. Rates of pathogenic/likely pathogenic mutations and variants of uncertain significance (VUS) were compared according to patient demographic and disease characteristics. 

Results:

Overall, 310 patients underwent testing, including 139 men with metastatic PC and 171 with localized PC. Median age was 68 (24-99). 203 underwent testing at Michigan Medicine and 107 at MIU. 92% of patients were Caucasian. In metastatic PC patients, rates of pathogenic/likely pathogenic GM were 10.8% vs. 14.6% for localized PC patients. The most common mutations were in CHEK2 (27%), ATM(12%) and BRCA2(10%).

Conclusion:

A large proportion of men with PC have mutations in key DNA damage repair genes. Screening all PC patients (irrespective of stage) and performing genetic testing for those with personal and family history meeting NCCN guidelines would increase identification of carriers, with potential implications for management of patients with metastatic or localized disease and cascade testing of at-risk family members. 

Funding: N/A