Long-term follow-up of facilitated cascade genetic testing for familial cancer syndromes: do at-risk relatives act on the information gained and what are the quality of life implications?

Objectives: In a pilot study, we found that facilitated cascade genetic testing for cancer-associated pathogenic mutations with telephone counseling and mailed saliva kits resulted in testing of 58% of at-risk relatives (ARRs), significantly higher than prior reports. To ascertain the true value of cascade testing, we must determine whether ARRs act upon information gained to prevent cancer morbidity and mortality. We aim to evaluate whether detecting the familial pathogenic mutations in ARRs resulted in utilization of genetically targeted cancer prevention and assess long-term quality of life. Methods: ARRs found on cascade genetic testing to harbor a pathogenic mutation were contacted two years following testing for telephone interviews. Interviews focused on utilization of guideline-based cancer preventative medical services, additional testing of family members and quality of life (QOL), assessed via three validated survey instruments (Hospital Anxiety and Depression Scale (HADS), Satisfaction with Decision Scale (SDS) and The Multidimensional Impact of Cancer Risk Assessment Questionnaire (MICRA)). Results: Our pilot trial identified 28 ARRs with pathogenic mutations, among which 25 (89%) were contacted successfully for 2-year follow-up. A total of 4 ARRs (19%) had undergone a total of six risk-reducing surgeries as a result of testing results (hysterectomy with salpingo-oophorectomy-3, salpingo-oophorectomy-1, mastectomy-2). A total of 21 ARRs (75%) underwent 35 cancer surveillance interventions (Figure 1). A total of 5 patients (24%) reported that the genetic results affected their fertility planning and three were considering preimplantation genetic diagnosis. A total of 23 patients (92%) reported sharing their genetic testing results with relatives. A total of 12 patients (52%) reported that their testing resulted in additional testing of relatives. ARRs reported that 14 additional relatives underwent testing, 8 were found to carry the familial mutation, 6 of whom underwent cancer surveillance and one underwent risk-reducing surgery. At 2 years following cascade testing, surveys demonstrated low median levels of anxiety (HADS-A 3, IQR 6) and depression (HADS-D 0, IQR 1) and high levels of satisfaction with testing (MICRA 28, IQR 10, SDS 29, IQR 5). Download : Download high-res image (114KB) Download : Download full-size image Conclusions: Long-term follow-up of our pilot study of facilitated cascade testing for cancer-associated pathogenic mutations demonstrates that the majority of ARRs found to carry the familial mutation utilize recommended cancer surveillance interventions and many undergo risk-reducing surgery. Furthermore, we have detected a cascade of the cascade, whereby testing of ARRs leads to iterative rounds of testing of additional relatives who then also have the option for cancer risk reduction. A prospective randomized trial of cascade testing facilitated by the medical team versus standard of care proband-mediated tested is planned and will be critical to shaping the way that the oncology community approaches cascade testing.