Uptake and patient-related outcomes of mainstreaming genetic testing: a systematic review and meta-analysis

Abstract

Objective: Mainstreaming genetic testing refers to genetic testing for cancer susceptibility genes following cancer diagnosis, which is provided by nongenetic health professionals of the cancer-treating team. Mainstreaming can be used to guide cancer treatment and secondary cancer prevention in the patient and to identify carriers in the family members of patients who test positive through cascade testing. We aimed to assess uptake and patient-reported outcomes of mainstreaming genetic testing.

Data sources: We searched PubMed and the Cochrane Library from inception to June 2024.

Study eligibility criteria: Our population included adult patients offered mainstreaming genetic testing (intervention). Outcomes included testing uptake, satisfaction, decisional conflict/regret, anxiety, depression, and cancer-related distress.

Study appraisal and synthesis methods: We followed a prospective protocol according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (International Prospective Register of Systematic Reviews: CRD42023467312). Qualitative synthesis and random effects meta-analyses were performed. Quality assessment was performed using the Methodological Index for Non-Randomized Studies.

Results: Searches yielded 5314 studies; 29 studies (n=13,219) were included, of which 14 were on ovarian cancer (n=6039), 6 on breast cancer (n=4354), 3 on prostate cancer (n=772), 1 on endometrial cancer (n=302), and 5 on multiple cancers (n=1752). There were no studies for colorectal cancer. Pooled genetic testing uptake was 91% (95% confidence interval=86-96, I²=99.6%, n=5942) across all cancers. Unselected testing uptake was 95% (95% confidence interval=92-98, I²=98.4%, n=3946), while family history/clinical criteria-based testing uptake was 80% (95% confidence interval=63-97, I²=99.0%, n=1996). Uptake for ovarian cancer cases was 93% (95% confidence interval=88-98, I²=98.6%, n=2801), for breast cancer 95% (95% confidence interval=90-99, I²=94.78%, n=981), for endometrial cancer 99% (95% confidence interval=98-100, I²=0.0%, n=304), and for prostate cancer 73% (95% confidence interval=47-99, I²=98.8%, n=772). Pooled pretest 24.24 (95% confidence interval: 23.34-24.14, I²=93.0%) and post-test 16.11 (95% confidence interval: 15.27-16.96, I²=80.3%). Decisional Conflict Scale scores were low (3 studies, n=681), decreasing from pretest to post-test (P=.03). On qualitative synthesis, pretest and post-test satisfaction scores were high (14 studies, n=3093). Decisional regret (4 studies, n=393), pretest and post-test depression scales (2 studies, n=252), and post-test distress (5 studies, n=773) were low. There was variability in reported pretest (low to high, 4 studies, n=1079) and post-test anxiety (low to moderate, 5 studies, n=1231) and pretest distress (low to moderate, 2 studies, n=594).

Conclusion: Mainstreaming genetic testing uptake is associated with high uptake and satisfaction and low decision conflict, regret, and post-test distress. Quality and quantity of evidence across different types of cancers vary significantly.

Keywords: cancer; genetic testing; germline; mainstreaming; outcomes; uptake.