| Description |
Lynch syndrome is a familial cancer syndrome due to mutations in genes that protect genetic stability. Approximately 1.1 million people in the United States carry a mutation in one of these genes. Among carriers of a Lynch syndrome mutation, lifetime risks for endometrial cancer are as high as 60%, up to 80% for colorectal cancer, and elevated for multiple other cancer types. Fortunately, these risks can be substantially reduced among carriers by providing preventive and/or enhanced surveillance interventions, principally for colorectal and endometrial cancers. Identification of carriers within a family usually starts with testing individuals with either endometrial or colorectal cancer; this is called index case finding. Testing of family members of index cases to determine their carrier status is referred to as cascade screening. The most common testing protocol for index case finding in the United States begins with staining tumor tissue with the immunohistochemistry (IHC) assay. There are two other tests in this protocol, with multiple steps and hand-offs between them. Notably, there are two alternative index case finding protocols emerging from research, which require evaluation to determine their effectiveness. In all of these protocols, consenting of patients prior to the final diagnostic test is considered the standard of care. In Aims 1 and 2, we performed analyses to explore the effectiveness and efficiency of the IHC-based and two alternative protocols. We anticipated that the analyses would suggest the alternative protocols to be substantially superior to the IHC protocol, and if so, could drive a paradigm shift in the aforementioned consent process. Based on this reasoning, for Aim 3 we undertook a review and synthesis of the literature about the necessity for informed consent prior in this context. Our analyses confirmed that the two alternative index case finding protocols, a brief family history questionnaire and direct-to-sequencing, are more effective and efficient than the IHC protocol under any plausible scenario. Our review of the literature on the requirement for consent revealed multiple developments converging to challenge the current paradigm of consent in this context, with substantive implications for clinical practice. |
