Specialist oncological surgery for removal of the ovaries and fallopian tubes in BRCA1 and BRCA2 pathogenic variant carriers may reduce primary peritoneal cancer risk to very low levels.

Risk reducing bilateral salpingo-oophorectomy (RRBSO) is highly effective for the prevention of high grade serous ovarian cancer (HGSOC) in BRCA1/2 pathogenic variant carriers (PVCs), but does not completely eliminate future risk of primary peritoneal cancer (PPC). The requirement to completely remove fallopian tubes at RRBSO and carefully exclude occult cancer/serous tubal intraepithelial carcinoma (STIC) lesions may not have been appreciated historically. We calculated rates of HGSOC and PPC in confirmed BRCA1/2 PVCs registered on the regional database in those who did (cases) and did not (controls) undergo RRBSO after genetic testing. Expected annual rates of ovarian/peritoneal cancer were 1% for BRCA1 ≥35yr and 0.5% for BRCA2 ≥45yr. Follow up before 35/45yr was ‘risk free’ and lead time excluded RRBSO <35yr and <45 years for BRCA1 and BRCA2, respectively. Women were followed from personal mutation report (controls) or RRBSO (cases) to death, ovarian/peritoneal cancer, or last follow up, whichever was sooner. In total, 891 cases (BRCA1=468, BRCA2=423) and 1,302 controls had follow up ≥35yr (BRCA1=736) and ≥45yr (BRCA2=566), respectively, over a total of 7,261.1 risk eligible years (mean=8.15yr). Twenty-one occult ovarian cancers were found at RRBSO (2.4%), 16 at stage 1. Post RRBSO, 56.97 ovarian/peritoneal cancers were expected but only 3 were observed (HR=0.053;95%CI=0.013–0.14), with combined Kaplan-Meier analysis HR=0.029 (95%CI=0.009–0.100,p<0.001). Risk reduction was greater in specialist (HR=0.03;95%CI=0.001–0.13) compared to non-specialist centres (HR=0.11;95%CI=0.02–0.37)(p=0.07). In controls, 23.35 ovarian/peritoneal cancers were expected with 32 observed (HR=1.37;95%CI=0.95–1.91). RRBSO <35/<45yrs reduces the risk of ovarian/peritoneal cancer by 95% in BRCA1/2 PVCs and may be greater in specialist centres.