Outcomes of universal germline testing for men with prostate cancer in an Australian tertiary center

Abstract

Aim:The role of germline testing in prostate cancer is evolving and knowledge of an individual's genetic profile may be used to guide not only an assessment of their familial risk but also have prognostic and therapeutic implications. Although international guidelines have incorporated recommendations for germline testing in prostate cancer, there is little Australian data to guide referrals. The aim of this study is to review the frequency of relevant pathogenic mutations in an Australian center, their associated clinical factors and clinical impact. Methods:We conducted a single-center retrospective review of men with prostate cancer that undertook prospective germline testing using a targeted next generation sequencing panel. Results:Results for 100 men were analyzed. Median age at diagnosis was 62 years (range 43-84); 92% had metastatic disease at referral. A pathogenic mutation was confirmed in 9%, a likely pathogenic variant in 2% and a variant of uncertain significance in 15%. Age ≤60 years was associated with an increased risk for a pathogenic germline variant (P = 0.0096). Two of the nine (22%) with pathogenic variants went on to receive targeted treatment. Conclusions:In this single center study, the incidence of germline mutations in genes associated with DNA-repair was consistent with rates seen previously published international series of men with metastatic disease. A pathogenic variant was only seen in one patient >60 years of age and no man referred solely on the basis of age or high-risk localized disease had a relevant finding. K E Y W O R D Sgenetics, germline, prostate cancer

Guidelines for genetic testing in prostate cancer: a scoping review

“…Prostate cancer has a strong genetic component [8][9][10][11][12]. The proportion of prostate cancer attributable to hereditary factors is estimated to be between 5 and 15% [13].…”

“…For example, up to 15% of men with metastatic and 10% in men with localised prostate cancer have mutations in homologous recombination repair (HRR) genes, such as BRCA2, BRCA1, ATM, CHEK2, PALB2, and mismatch repair (MMR) genes (MLH1, MSH2, PMS2 and MSH6). Several inherited mutations (e.g., BRCA1 and BRCA2) are associated with varying degrees of increased predisposition to prostate cancer [8][9][10][11][12]. These mutations are linked with a younger age of cancer onset, an aggressive clinical course, and increased cancer mortality [14].…”