Cascade testing for hereditary cancer syndromes: Should we move towards direct relative contact? A systematic review and meta-analysis (384)

Abstract

<b>Objectives:</b> Evidence-based guidelines recommend cascade testing for hereditary cancer syndromes, as identifying relatives with a familial mutation provides the opportunity for early detection and prevention of cancer. The current standard is for patients to contact their relatives (patient-mediated contact) and encourage genetic testing. However, patient-mediated cascade testing accomplishes genetic testing for <30% of relatives, representing a significant missed public health opportunity. Direct relative contact by the medical team has shown promise for other, non-oncologic, genetic syndromes but is complicated by privacy laws and the lack of current infrastructure within the medical system. We sought to evaluate the literature on patient-mediated and direct relative contact for cancer cascade testing and determine if any specific interventions or patient characteristics drive the utilization of services. <b>Methods:</b> We searched key electronic databases to identify studies evaluating cascade testing for hereditary cancer syndromes. Eligible trials were subjected to meta-analysis, and the moderating influence of health interventions and patient characteristics on rates of genetic assessment were examined. The current study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was preregistered with PROSPERO (registration no.: CRD42020134276). <b>Results:</b> Forty-eight studies were included (15 reports on direct relative contact, 36 on patient-mediated contact, three on both scenarios). When relatives were contacted directly by the medical team, 58% (95% CI: 47%-68%) completed genetic testing versus 36% (95% CI: 28%-45%) when contact was mediated by the patient. Methods of direct contact by the medical team included letters, telephone calls, and emails. Among the entire cohort, the following patient characteristics were associated with greater uptake of cascade testing: female versus male gender, first-degree relation versus more distant relation, and Lynch syndrome versus <i>BRCA1/2</i> (Table 1). Among families relying on patient-mediated contact, the use of an information aid resulted in 41% [95% CI: 31%-52%] completion of cascade testing versus 34% [95% CI: 24%-45%] without an information aid. <b>Conclusions:</b> The majority of relatives at risk for hereditary cancer syndromes do not undergo cascade testing and, therefore, forgo potentially life-saving medical interventions. Direct relative contact by the medical team results in higher completion rates of cascade testing than patient-mediated cascade testing. These data argue for a paradigm shift, whereby the medical system works with patients, respecting privacy laws while also offering methods for direct relative contact. Furthermore, cascade programs must consider the populations who currently are less likely to complete cascade testing, including males and <i>BRCA1/2</i> families.