Improving calculation, interpretation and communication of familial colorectal cancer risk: Protocol for a randomized controlled trial

Contains fulltext : 88114.pdf (publisher's version ) (Open Access)BACKGROUND: Individuals with multiple relatives with colorectal cancer (CRC) and/or a relative with early-onset CRC have an increased risk of developing CRC. They are eligible for preventive measures, such as surveillance by regular colonoscopy and/or genetic counselling. Currently, most at-risk individuals do not follow the indicated follow-up policy. In a new guideline on familial and hereditary CRC, clinicians have new tasks in calculating, interpreting, and communicating familial CRC risk. This will lead to better recognition of individuals at an increased familial CRC risk, enabling them to take effective preventive measures. This trial compares two implementation strategies (a common versus an intensive implementation strategy), focussing on clinicians' risk calculation, interpretation, and communication, as well as patients' uptake of the indicated follow-up policy. METHODS: A clustered randomized controlled trial including an effect, process, and cost evaluation will be conducted in eighteen hospitals. Nine hospitals in the control group will receive the common implementation strategy (i.e., dissemination of the guideline). In the intervention group, an intensive implementation strategy will be introduced. Clinicians will receive education and tools for risk calculation, interpretation, and communication. Patients will also receive these tools, in addition to patient decision aids. The effect evaluation includes assessment of the number of patients for whom risk calculation, interpretation, and communication is performed correctly, and the number of patients following the indicated follow-up policy. The actual exposure to the implementation strategies and users' experiences will be assessed in the process evaluation. In a cost evaluation, the costs of the implementation strategies will be determined. DISCUSSION: The results of this study will help determine the most effective method as well as the costs of improving the recognition of individuals at an increased familial CRC risk. It will provide insight into the experiences of both patients and clinicians with these strategies.The knowledge gathered in this study can be used to improve the recognition of familial and hereditary CRC at both the national and international level, and will serve as an example to improve care for patients and their relatives worldwide. Our results may also be useful in improving healthcare in other diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00929097

Adding family history to faecal immunochemical testing increases the detection of advanced neoplasia in a colorectal cancer screening programme

Background Faecal immunochemical testing (FIT) for colorectal cancer (CRC) screening has suboptimal sensitivity for detecting advanced neoplasia. To increase its performance, FIT could be combined with other risk factors. Aim To evaluate the incremental yield of a screening programme using a positive FIT or a CRC family history, to offer a diagnostic colonoscopy. Methods For this post hoc analysis, data were collected in the colonoscopy arm of a colonoscopy or colonography for screening study. In this study, 6600 randomly selected, asymptomatic men and women (50–75 years) were invited for screening colonoscopy. 1112 Participants completed a FIT and a questionnaire prior to colonoscopy. We compared the yield of FIT-only and FIT combined with CRC family history, defined as having one or more first-degree relatives with CRC. Results At a 10 μg Hb/g faeces FIT-positivity threshold the combined strategy would increase the yield from 36 (3.2%; CI: 2.4–4.5%) to 53 (4.8%; CI: 3.7–6.2%) cases of advanced neoplasia, at the expense of 148 additional negative colonoscopies. Sensitivity in detecting advanced neoplasia would increase from 36% (CI: 26–46%) to 52% (CI: 42–63%), whereas specificity would decrease from 93% (CI: 92–95%) to 79% (CI: 76–81%). The strategy will be preferred if one accepts 8.8 false positives for every additional participant in whom advanced neoplasia can be detected. Conclusions Offering colonoscopy to those with a positive FIT or CRC family history increases the yield of a FIT-based screening programme. Depending on the number of negative colonoscopies one accepts, this combined approach can be considered for improving CRC screening

Evaluation of yield and experiences of age‐related molecular investigation for heritable and nonheritable causes of mismatch repair deficient colorectal cancer to identify Lynch syndrome

Contains fulltext : 225442pub.pdf (publisher's version ) (Open Access)Universal mismatch repair deficiency (dMMR) testing of colorectal cancer (CRC) is promoted as routine diagnostics to prescreen for Lynch syndrome. We evaluated the yield and experience of age-related molecular investigation for heritable and nonheritable causes of dMMR in CRC below age 70 to identify Lynch Syndrome. In a prospective cohort of 3602 newly diagnosed CRCs below age 70 from 19 hospitals, dMMR, MLH1 promoter hypermethylation, germline MMR gene and somatic MMR gene testing was assessed in daily practice. Yield was evaluated using data from the Dutch Pathology Registry (PALGA) and two regional genetic centers. Experiences of clinicians were evaluated through questionnaires. Participating clinicians were overwhelmingly positive about the clinical workflow. Pathologists routinely applied dMMR-testing in 84% CRCs and determined 10% was dMMR, largely due to somatic MLH1 hypermethylation (66%). Of those, 69% with dMMR CRC below age 70 without hypermethylation were referred for genetic testing, of which 55% was due to Lynch syndrome (hereditary) and 43% to somatic biallelic pathogenic MMR (nonhereditary). The prevalence of Lynch syndrome was 18% in CRC < 40, 1.7% in CRC age 40-64 and 0.7% in CRC age 65-69. Age 65-69 represents most cases with dMMR, in which dMMR due to somatic causes (13%) is 20 times more prevalent than Lynch syndrome. In conclusion, up to age 65 routine diagnostics of (non-)heritable causes of dMMR CRCs effectively identifies Lynch syndrome and reduces Lynch-like diagnoses. Above age 64, the effort to detect one Lynch syndrome patient in dMMR CRC is high and germline testing rarely needed