Selection process and screening invitation
CRC
At least 3 months after the diagnosis of CRC, and once oncologic surgery had been performed, index cases were contacted by phone to arrange an appointment at the high-risk CRC clinic office of each participating center. In the interviews, they were informed of the objectives of the study and were asked to sign an informed consent. If the index case met the inclusion criteria, a family tree of the first generation (parents, offspring, or siblings) was generated to identify all eligible and living relatives. At this point, an open-label randomization (1:1) was performed in FDR to undergo FIT for 3 consecutive years, and work-up colonoscopy if a positive test occurred, or straightforward colonoscopy. This was done using the randomization module in RedCap Electronic Data Capture (REDcap) [In the same interview, the index case received a personal invitation letter for each eligible family member and was asked to hand it to them. This letter described the importance of CRC prevention, provided a detailed written description of the aims, and included a formal invitation to participate in the assigned study group. A phone number was provided to the index case and eligible FDR to contact a member of the high-risk CRC clinic office at any time to schedule the enrollment appointment conveniently. Eligible individuals were given a leaflet with detailed information on the study outcomes, as well as the advantages and disadvantages of the assigned screening strategy. They were aware that they were part of a randomized study, and that colonoscopy is the standard approach for high-risk families. Those who did not attend the appointment were sent a reminder letter through the index case 2 months later.