Prospective Feasibility Trial of a Novel Strategy of Facilitated Cascade Genetic Testing Using Telephone Counseling

Abstract

PURPOSE A powerful consequence of detecting cancer-associated pathogenic variants is the ability to test at-risk relatives (ARRs), termed cascade testing. However, historical studies suggest cascade testing uptake of 30% or less. Here, we tested the feasibility of a novel, streamlined method of cascade testing using telephone genetic counseling and mailed saliva-based genetic testing. PATIENTS AND METHODS Probands with newly diagnosed cancer-associated pathogenic variants were offered facilitated cascade testing whereby the genetics team identified and contacted ARRs by telephone to disclose the familial pathogenic variant and offer telephone counseling and mailed saliva testing. Results and guideline-based recommendations were reviewed by telephone and shared with the primary care physician. RESULTS Thirty probands were enrolled, and 114 ARRs were identified. Twelve ARRs were excluded (lived outside of the United States, n = 5; proband did not approve of contact, n = 7). Among 102 ARRs telephoned, contact was established with 95 (93%). Among 114 identified ARRs, 66 (58%) completed genetic testing. Among those completing testing, 27 (41%) carried the familial pathogenic variant. Surveys of ARRs at the time of genetic testing and 6 months later demonstrated low levels of anxiety, depression, distress, and uncertainty and high levels of satisfaction with testing. At 6 months, 7 ARRs with pathogenic variants had undergone cancer surveillance interventions and 4 had undergone cancer risk-reducing surgery. CONCLUSION Facilitated cascade testing with telephone genetic counseling and mailed saliva kits resulted in high testing uptake among ARRs. Positive genetic testing resulted in utilization of genetically targeted primary disease prevention at short-term follow-up. Facilitated cascade testing is a straightforward, low-cost, easily implemented strategy with significant potential to promote early detection for affected ARRs and reduce cancer mortality and should be evaluated in larger scale clinical trials.

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“…Despite the high pretest probability of detecting a P/LP variant, the relatively low cost and the straightforward interpretation (without VUS), uptake of cascade testing in family members at risk of a cancer predisposition has typically been suboptimal. Previous studies in adult cancer predisposition have generally found that approximately half of at-risk first-degree relatives undergo cascade testing 33 , with more recent initiatives investigating practices to identify and reduce burdens on family members to increase uptake 16,[34][35][36] . Uptake in our cohort was similarly low, although variable based on penetrance of the variant as well as the gene itself (that is, a low cascade testing rate for NF1 is unsurprising given that the diagnosis or absence of a diagnosis can typically be made clinically in relatives).…”

Interventions Facilitating Family Communication of Genetic Testing Results and Cascade Screening in Hereditary Breast/Ovarian Cancer or Lynch Syndrome: A Systematic Review and Meta-Analysis

“…Meta-analysis of outcomes was possible only for 13 studies, and not all of them had assessed family communication of test results and/or cascade genetic testing of relatives as a primary outcome. Our literature search identified serendipitously additional papers describing the development of relevant interventions [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. However, none of them had been rigorously tested with an RCT, indicating that the scientific field is still in development.…”

“…However, removing this barrier does not guarantee successful cascading of blood relatives due to the resources needed to identify, contact, and counsel them. Additional measures, such as mailing of saliva kits [ 64 ] and family-based telephone or web-based counseling, hold promise to enhance cascade genetic testing and improve individual and population health outcomes.…”

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“…As one study shows, 68.4% of minority women completed testing after a telephone session, as compared with 87% completion within non-Hispanic white participants (Butrick et al, 2015). In other studies that have taken measures to lower barriers to sample collection, however, increased testing uptake among participants after telephone genetic counseling is reported (Frey et al, 2020).…”