A systematic review and meta-analysis of genetic assessment for women with ovarian cancer: how can we do better?

Objectives: Despite clear consensus guidelines recommending universal germline genetic testing in ovarian cancer patients and a growing appreciation of the significant health implications for patients and their relatives, fewer than 50% of women with ovarian cancer undergo genetic testing. We aim to use systematic review and meta-analysis to assess the status of genetic testing in ovarian cancer and identify strategies that can improve uptake of genetic assessment in this high-risk population. Methods: A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for studies reporting on genetic testing in ovarian cancer without date restriction was performed. Random effects pooled proportions were calculated using the logit transformation and 95% confidence intervals for individual study proportions were calculated using the Clopper-Pearson exact method. Results: The comprehensive search produced 3026 studies, among which 38 met inclusion criteria. Among studies listing mean age of diagnosis, stage, and histology data, the median of the mean age of diagnoses across the studies was 60.5 years. The median proportion of patients with early stage (I/II) ovarian cancer was 22.8%, late stage (III/IV) 70%, and unknown stage 3.6%. The median proportion of patients with serous histology was 74.6%, endometrioid 8.6%, mucinous 6%, clear cell 7%, mixed 3.6%, carcinosarcoma 3.4%, adenocarcinoma 5.8%, and other/unknown histology 7.9%. Twenty-one papers described rates of referral to genetic counseling and found, among 9,629 women, a referral rate of 56% [CI 32-78%]. Twenty-three papers described genetic testing uptake without a specified intervention and found, among 16,412 women, 34% [CI 23-47%] underwent genetic testing (Figure 1). For patients completing genetic testing, 27% [CI 22-32%] had a pathogenic mutation and 7% [CI 3-16%] a variant of uncertain significance. The most successful strategy aimed at improving rates of genetic testing was ‘mainstreaming,’ the process of providing counseling and testing in the oncology clinic by trained non-genetics specialists. With mainstreaming, 99% [CI 86-100%] of patients completed genetic testing. Other strategies described in the literature included the use of telemedicine for genetic services (75% underwent genetic testing [CI 43-93%]), embedding a genetic counselor in the clinic (67% [CI 32-90%]), reflex somatic tumor BRCA1/2 testing to triage to germline testing (64% [17-94%]), practice recommendation for universal testing of all ovarian cancer patients (42% [CI 15-74%]), and incorporating dedicated referral forms into practice (26% [CI 10-53%]). Download : Download high-res image (203KB) Download : Download full-size image Conclusions: Identifying causative germline mutations in ovarian cancer can impact treatment decisions, inform risk of other malignancies and guide disease prevention and early detection in at-risk relatives. Rates of both referral to genetic counseling and testing remain low, 56% and 34% respectively, despite broad recommendations for universal testing. Mainstreaming, use of telemedicine, embedding genetic counselors in the clinic, and triage via reflex somatic BRCA1/2 assessment are all strategies demonstrating success in this patient population and should be considered for those providing care to women with ovarian cancer.