Direct letters to relatives at risk of hereditary cancer – study protocol for a multi-centre randomised controlled trial of healthcare-assisted versus family-mediated risk disclosure at Swedish cancer genetics clinics (DIRECT-study)

Abstract

Background: The results of genetic investigation for hereditary cancer are of importance to the individual patients, but also to their genetic at-risk relatives. Standard care is to encourage the proband (first family member under investigation) to pass on this risk information to the relatives. Previous research suggests that with family-mediated disclosure only about a third of at-risk relatives contact health care to receive genetic counselling. In some studies, complementing family-mediated risk disclosure with healthcare-assisted risk disclosure almost doubles the uptake of genetic counselling in at-risk relatives. In this study we evaluate healthcare-assisted direct letters to relatives at risk of hereditary cancer syndromes in a randomised controlled trial. Methods: Probands are recruited from Swedish outpatient cancer genetics clinics to this two-arm randomised controlled trial. The study recruits probands with either a pathogenic variant in a cancer susceptibility gene (BRCA1, BRCA2, PALB2, MLH1, MSH2/EPCAM, MSH6, PMS2) or probands with familial breast and colorectal cancer based on clinical and pedigree criteria. In both arms probands receive standard care, i.e., are encouraged and supported to pass on information to relatives. In the intervention arm, the proband is also offered to have direct letters sent to the at-risk relatives. The primary outcome measure is the proportion of at-risk relatives contacting a Swedish cancer genetics clinic within 12 months of the proband receiving the test results. Discussion: This paper describes the protocol of a randomised controlled clinical trial evaluating a healthcare-assisted approach to risk disclosure by offering the probands to send direct letters to their at-risk relatives. The results of this study should be informative in the future development of risk disclosure practices in cancer genetics clinics. Trial registration; ClinicalTrials.gov Identifier NCT04197856 (pre-trial registration on December 13, 2019). • https://clinicaltrials.gov/ct2/show/NCT04197856?id=NCT04197856&draw=2&rank=1&load=cart Also registered at the website “RCC Cancerstudier i Sverige” as study #86719).