China Colorectal Cancer Screening Trial 2 (C-Cost2)

This study intends to recruit participants who meet the above inclusion and exclusion criteria in China, with the goal of recruiting at least 7504 eligible participants at baseline. The study adopts an individual-level randomized design. After signing the informed consent form, eligible participants will be randomly assigned to 2 colorectal cancer screening groups. All participants will undergo a 4-year screening phase, and then all participants will be followed up for a long term. Fecal, blood, and tissue samples will be collected from the participants during the study. The grouping and specific intervention measures are as follows:

• FIT group (n = 3752): The internationally recommended screening protocol is adopted. In the first 4 years of the screening phase, all participants will receive annual FIT tests. Participants with positive FIT results are recommended to undergo diagnostic colonoscopy. Suspicious lesions detected during the colonoscopy will be resected and further sent for pathological examination. Participants who refuse FIT tests, have negative FIT tests, have positive FIT tests but do not receive diagnostic colonoscopy will be screened again in the first 4 years. All the participants will be followed by long-term follow-ups.
• FIT-sDNA group (n = 3752): A new screening protocol is adopted. In the first 4 years of the screening phase, all participants will receive annual FIT-sDNA tests. Participants with positive FIT-sDNA results are recommended to undergo diagnostic colonoscopy. Suspicious lesions detected during the colonoscopy will be resected and further sent for pathological examination. Participants who refuse FIT-sDNA tests, have negative FIT-sDNA tests, have positive FIT-sDNA tests but do not receive diagnostic colonoscopy will be screened again in the first 4 years. All the participants will be followed by long-term follow-ups.

Inclusion criteria

• Age: 45-74 years old;
• In good general condition, with normal mental state and voluntarily signing the informed consent form;

Exclusion criteria

• Personal history of colorectal cancer or precancerous lesions;
• History of previous colonrectal resection surgery;
• Diagnosed with cancer before enrollment or currently receiving any cancer-related treatment;
• Having received colonoscopy, flexible sigmoidoscopy, CT colonography and other examinations within the past 5 years;
• Having received FIT or FIT-sDNA or cfDNA test within the past 1 year;
• Symptomatic lower gastrointestinal diseases or symptoms suggesting the need for diagnostic colonoscopy for confirmation;
• Accompanied by severe diseases that are not suitable for colorectal cancer screening;