Direct to patient testing at cancer diagnosis for precision prevention-2 (DETECT-2): protocol for a 2-arm equivalence UK multi-center randomized controlled trial evaluating uptake of genetic testing

BACKGROUND: Mainstreaming patients with ovarian, endometrial, and colorectal cancer in the context of genetic testing at cancer diagnosis involves pre-test counseling, consent, and return of results by the clinical cancer team. This process uses significant clinician time and resources. Alternative implementation strategies might be more cost-efficient and better utilize limited cancer health professional and genetics workforce resources, but their efficacy is less well understood. PRIMARY OBJECTIVE: To determine if direct-to-patient genetic testing for ovarian, endometrial, and colorectal cancer has equivalent uptake of genetic testing compared with mainstreaming. STUDY HYPOTHESIS: Patients at ovarian, endometrial, or colorectal cancer diagnosis have equivalent uptake for genetic testing through direct-to-patient compared with mainstreaming. TRIAL DESIGN: A multicenter randomized controlled trial evaluating a digitally enabled direct-to-patient (saliva-based, at home) genetic testing approach (intervention arm) compared with mainstreaming genetic testing (control arm). After study consent and randomization, patients in the direct-to-patient arm are offered access to an app-based decision aid, consent to genetic testing via the app, and access to a helpline for additional support and counseling if needed. Control arm participants are offered routine mainstreaming genetic testing in the clinic. We include a qualitative sub-study of 1:1 interviews to understand the attitudes, experiences, and impact on emotional well-being of patients undergoing genetic testing. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria include diagnosis of ovarian, endometrial, or colorectal cancer fulfilling the National Health Service clinical genetic testing criteria. Exclusion criteria include prior genetic testing for or a known familial pathogenic variant in ovarian, endometrial, or colorectal cancer susceptibility genes. PRIMARY ENDPOINT: Absolute difference in uptake of genetic testing between arms in the intention-to-treat population, with equivalence determined using a 10% margin based on a 2-sided 95% confidence interval. SAMPLE SIZE: Target n = 626 to 832 patients. We will test equivalence if ≥626 patients are recruited in the intention-to-treat population. ESTIMATED DATE FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Recruitment by December 2026 and publication of results in 2028. TRIAL REGISTRATION: ISRCTN:57402067 (July 26, 2023). (https://doi.org/10.1186/ISRCTN57402067).