Combining Risk Factors and Faecal Immunochemical Testing in Colorectal Cancer Screening: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6,753
- 试验地点
- 2
- 主要终点
- Yield of Advanced Neoplasia
研究概览
简要总结
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.
详细描述
INTRODUCTION AND RATIONALE Colorectal Cancer (CRC) is the third most frequent diagnosed cancer worldwide, with 1.4 million new cases every year. Mortality of CRC is estimated at around 40%. To reduce the incidence of CRC and to abate the negative consequences associated with CRC, methods for early detection of (pre)malignant colorectal lesions have extensively been researched and implemented. Colonoscopy is the reference standard for the detection of advanced neoplasia, but it requires trained endoscopists, carries a high burden, harbours a risk for complications in patients, and increases societal costs.
Most screening programs use methods to select screening participants with a high risk of advanced neoplasia for colonoscopy. One such method is the detection of blood in stool with faecal immunochemical tests (FITs).
Multiple nation-wide screening programs have now been implemented using FIT, including one in the Netherlands. In the Dutch CRC screening program, using a FIT threshold of 47 µg Hb/g faeces, the sensitivity of FIT in detecting CRC is 85.5%. The sensitivity of FIT in detecting advanced neoplasia (AN) is however substantially lower: 38%.
FIT-based screening also generates a high number of false positives, leading to unnecessary colonoscopies and distress for those patients. Approximately 1 in 2 FIT-positives has advanced neoplasia; the first round of the Dutch CRC screening program, using a FIT threshold of 47 µg Hb/g faeces, reached a positive predictive value of 54%.
Previous studies have demonstrated the existence of clinical risk factors for CRC, such as male gender, age, family history of CRC, and smoking. In a ZonMW sponsored project (ZonMW 50-50115-96-521) our group has shown that higher age, male sex, a family history with close relatives in whom CRC was diagnosed, and active smoking were all associated with the presence of advanced neoplasia (Stegeman et al, Gut, 2014).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In order to be eligible to participate in this study, a screening invitee must meet the following criteria:
- •The screening invitee must be at least 55 years old, and no older than 75 years old, at the day of invitation by the Foundation of Population Screening Mid-West
- •The screening invitee must be eligible for participation in the second round of the Dutch CRC Population Screening Programme
- •The screening invitee must return a signed informed consent form
排除标准
- •A potential screening invitee who meets any of the following criteria will be excluded from participation in this study:
- •if he or she receives active treatment for CRC and/or AN, including palliative care.
- •if he or she fails to return a sample that is adequate for FIT testing.
结局指标
主要结局
Yield of Advanced Neoplasia
时间窗: 10 weeks
The primary outcome is the yield of advanced neoplasia, defined as the relative number of invitees in whom advanced neoplasia is detected at colonoscopy.
次要结局
- Yield of Advanced Neoplasia at Other Thresholds(10 weeks)
- Yield of Proximally Located Advanced Neoplasia(10 weeks)
- Participation Rate(10 weeks)
- Standardized Screening Yield(10 weeks)
研究者
Prof. Evelien Dekker, MD, PhD
Professor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)