Combining Risk Factors and Faecal Immunochemical Testing in Colorectal Cancer Screening: a Randomized Controlled Trial

Colorectal Carcinoma (CRC) is the third most frequent diagnosed cancer worldwide, with 1.4 million new cases every year. In an attempt to reduce this number many countries have implemented a nationwide screening programme targeted at detecting CRC in an early phase using fecal immunochemical tests (FITs). People with an elevated level of blood in their stool are offered a colonoscopy, an invasive medical procedure where CRCs and premalignant lesions (together also referred to as advanced neoplasia) can be detected accurately.
However, the current screening method using FIT is not optimal. In FIT-based CRC screening studies, 1 in 4 participants with CRC and 2 in 3 participants with advanced neoplasia receive a negative FIT result. In contrast, an estimated 1 in 2 FIT-positives have advanced neoplasia at colonoscopy.
Recent studies have demonstrated that a risk model that takes into account the FIT result and other risk factors for CRC could enhance the effectiveness of a FIT-based CRC screening programme.
The objective of this study is to assess the yield of advanced neoplasia in the colon and rectum of a FIT-based risk model at colonoscopy, compared to that of a FIT-only CRC screening strategy. Our hypothesis is that a risk-based model yields significantly more advanced neoplasia at colonoscopy than the FIT by itself, and that it does not affect participation rate.
To assess this hypothesis, the investigators have designed a clinical trial in which the investigators randomize 23,000 asymptomatic individuals between the age of 55 and 75 years old to either risk-based screening (intervention group) or FIT-only screening (control group). The intervention group will receive a questionnaire on risk factors of CRC (e.g. smoking, family history of CRC), and a FIT. The control group will only receive the FIT. The positivity threshold of the FIT in both groups will be set at 15 micrograms haemoglobin per gram faeces. The positivity threshold of the risk-based model in the intervention group will be set at 0.10 (out of a range of 0 to 1), a threshold that is calculated with a goal to match the positivity rate of the control group.
Participants with a result that is above the thresholds of the FIT and/or the risk-based model will be invited to undergo a colonoscopy according protocol of the Dutch national screening program. After the study has ended, the investigators will compare both groups to assess our hypotheses.

结直肠癌（Colorectal Carcinoma, CRC）是全球第三大高发确诊癌症，每年新增病例达140万例。为降低这一发病数字，多国已启动全国性筛查计划，旨在通过粪便免疫化学检测（Fecal Immunochemical Tests, FITs）在疾病早期阶段检出结直肠癌。粪便隐血水平升高的受试者将被建议接受结肠镜检查——这是一种有创医疗操作，可精准检出结直肠癌及癌前病变（二者合称为进展期瘤变）。然而，当前基于FIT的筛查方案并非最优选择。在基于FIT的结直肠癌筛查研究中，每4名结直肠癌患者中便有1人、每3名进展期瘤变患者中便有2人获得FIT假阴性结果。与之形成对比的是，据估算每2名FIT阳性受试者中，便有1人在结肠镜检查中被检出进展期瘤变。近期已有研究证实，结合FIT结果与其他结直肠癌风险因素的风险模型，可有效提升基于FIT的结直肠癌筛查方案的效能。本研究的目标为：对比基于风险模型的结肠镜检查进展期瘤变检出率与仅基于FIT的结直肠癌筛查策略的检出率。我们的假说为：相较于单独使用FIT筛查，基于风险模型的方案可在结肠镜检查中检出更多进展期瘤变，且不会对筛查参与率造成影响。为验证该假说，研究人员设计了一项临床试验，将23000名年龄介于55至75岁的无症状受试者随机分配至两组：基于风险的筛查组（干预组）与仅FIT筛查组（对照组）。干预组受试者将填写结直肠癌风险因素调查问卷（如吸烟史、结直肠癌家族史）并接受FIT检测；对照组仅需接受FIT检测。两组FIT检测的阳性阈值均设定为每克粪便中血红蛋白含量15微克。干预组中风险模型的阳性阈值设定为0.10（取值范围为0至1），该阈值的设置目标为匹配对照组的阳性率。凡FIT阈值和/或风险模型阈值呈阳性的受试者，将按照荷兰国家筛查方案的流程受邀接受结肠镜检查。研究结束后，研究人员将对两组数据进行对比分析，以验证前述假说。