A Stool DNA Test for Detection of Advanced Colorectal Neoplasia in Asymptomatic Chinese Community Population

A Stool DNA Test vs. Fecal Immunochemical Test for Detection of Advanced Colorectal Neoplasia in Asymptomatic Chinese Population and Potential Uses of a Risk-scoring System: A Multi-central Community-based Screening Study

Sponsors

Lead Sponsor: Changhai Hospital

Collaborator: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Gongli Hospital of Shanghai Pudong New Area
Shanghai Songjiang District Central Hospital
Shanghai Jing'an District Central Hospital
Shanghai Yangpu District Central Hospital
People's Hospital of Qingyuan
Guangdong Provincial Hospital of Traditional Chinese Medicine
900 Hospital of the Joint Logistics Team
First Affiliated Hospital of Suzhou Medical College
Affiliated Hospital of Jiangnan University
Affiliated Hospital of Jiangsu University
Yangzhou Fisrt People's Hospital
Traditional Chinese Medicine Hosipital of Kunshan
Ankang Central Hospital
Shandong Cancer Hospital

Source Changhai Hospital
Brief Summary

To compare the performance of stool-based SDC2 DNA methylation test and commercially available Fecal Immunochemical Test (FIT) for detection of advanced colorectal neoplasia and other precancerous lesions in the asymptomatic Chinese community population. The potential uses of a risk-scoring system (APCS) would be evaluated too.

Detailed Description

In China, colorectal cancer (CRC) remains to be the leading cancer of the digestive system. According to nationwide cancer statistics using population-based cancer registry data in China, age-standardized incidence rate of CRC and age-standardized mortality rate increased significantly from 2000 to 2015. It induces a substantial financial burden in terms of healthcare utilization and quality-adjusted life years (QALY) lost. Fecal Occult Blood Tests (FOBT) and colonoscopy have been proposed as the main primary screening modalities for asymptomatic subjects by international guidelines and Asia Pacific Consensus Statements. Nevertheless, shortage and uneven distribution of colonoscopy resources combined with huge population base consisted of the current situation in China. Previous population-based CRC screening programs usually employed questionnaires and/or FOBT to assess high-risk groups and recommended colonoscopy. This algorithm faced difficulties such as complex traditional questionnaires, low colonoscopy adherence, and a high false-positive rate. When the Coronavirus disease 2019 pandemic further limited the implementation of colonoscopy, the contradictions developed more acute. A Hong Kong group had designed and validated a colorectal cancer risk scoring system based on age, gender, smoking history, and family history through the results of screening in 11 Asia-Pacific cities. The Asia-Pacific Colorectal Screening (APCS) score was more concise and divided the population into three categories: low risk, intermediate risk, and high risk. Compared with the low-risk population, the probability of advanced colorectal neoplasia in intermediate-risk and high-risk population increased by 2.6 times and 4.3 times respectively. Because of simplicity and efficiency, it was recommended by Asia-Pacific screening guidelines and several guidelines in China. Another APCS related multi-center study indicated that by selecting high-risk subjects and low/average-risk subjects with a positive fecal immunochemical test (FIT) for colonoscopy, the colonoscopy workload could be reduced by 50% compared with the strategy of primary colonoscopy in those same subjects. All these experiences deserved to be drawn on during the post-pandemic era. The recent decade has witnessed a rapid development of non-invasive biomarkers to detect CRC. Stool DNA(sDNA) Testing is a novel screening test for CRC, using molecular techniques to identify CRC-relevant biomarkers in stool. One of its toolkits, Multitarget Stool DNA Testing (FIT-DNA), was first approved by the FDA in 2014 for its application in clinical practice, which has been widely promoted in the United States. Subsequently, it was endorsed by multiple societies as one of the recommended screening tests. Recently, a stool test of methylated Syndecan-2(SDC2) has been developed as a fecal-DNA product targeted to improve the diagnostic accuracy of CRC screening. A meta-analysis of previous clinical studies reporting the accuracy of stool DNA methylation tests in detecting CRC included 46 studies totaling 16,149 patients. The most accurate single gene was found to be SDC2 with a pooled sensitivity of 83.1% (72.6%, 90.2%) and a specificity of 91.2% (88.6%, 93.2%). A recent study involving 1,110 subjects from 2017 to 2018 by three Chinese tertiary hospitals assessed the performance of the SDC2 sDNA test. The sensitivity of the SDC2 sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early-stage CRC (stage I-II), while maintaining a specificity of 699/713 (98.0%). Nevertheless, there were limitations in the design of these original studies. For instance, most involved small, hospital-based CRC cases and controls that might not fill the knowledge gap between population screening. Additional clinical trials are required to further validate its diagnostic accuracy in other populations, especially community-setting. Our study intends to include asymptomatic subjects from the communities along the southeast coast of China. Potential participates would be randomly recruited via community public communication. The subjects would be asked to fill in a concise questionnaire obtained through a public WeChat account after informed consent. Basic information would be acquired while APCS score and correspondent risk categories would be calculated automatically. After sampling education (on-site + online), stool collection devices of sDNA and quantitative fecal immunochemical test (qFIT) would be distributed to all subjects. Two samples of stool from single defecation would be requested to put into the two collection devices according to instructions respectively by the subjects themselves at home. Efforts would be made by the public WeChat account and the community staff to urge samples recover from subjects as quickly as possible (prefer within 24h after defecation. Later than 5 days would be deemed ineligible). Community staff would deliver the samples qualified in the initial evaluation to the standardized laboratory for testing as quickly as possible. If APCS be evaluated high-risk or any of qFIT or sDNA tests positive, the risk of the subject would be considered increased. Colonoscopy would be strongly recommended, and priority and rapid arrangement would be made in the corresponding center. For subjects with low/intermediate-risk APCS and negative qFIT and sDNA, the project team also encourages the subjects to accept colonoscopy on the basis of a clear understanding of benefits and risks. We would help to arrange colonoscopy as early as possible. All colonoscopy examinations would be performed in the designated endoscopy centers by experienced endoscopists while monitoring quality of colonoscopy (bowel preparation, cecal intubation rate and withdrawal time). Full-time recording personnel would be arranged to follow up and record the relevant information of colonoscopy. For the subjects diagnosed with colorectal cancer, the postoperative diagnosis and tumor-node-metastasis (TNM) staging of the subjects would be retrieved.

Overall Status Recruiting
Start Date 2021-03-22
Completion Date 2021-12-31
Primary Completion Date 2021-12-31
Study Type Observational
Primary Outcome
Measure Time Frame
Sensitivity and specificity of sDNA vs qFIT in the detection of advanced colorectal neoplasia Through study completion, an average of 1 year
Secondary Outcome
Measure Time Frame
Positive predictive value and negative predictive value of sDNA vs qFIT in the detection of advanced colorectal neoplasia Through study completion, an average of 1 year
Sensitivity and specificity of sDNA vs qFIT in the detection of colorectal cancer, advanced adenoma, advanced serrated lesion, and colorectal adenoma. Through study completion, an average of 1 year
Positive predictive value and negative predictive value of sDNA vs qFIT in the detection of colorectal cancer, advanced adenoma, advanced serrated lesion, and colorectal adenoma. Through study completion, an average of 1 year
The efficacy of sDNA in the detection of colorectal cancer and precancerous lesion in high-risk asymptomatic community population. Through study completion, an average of 1 year
The efficacy of sDNA in the detection of colorectal cancer and precancerous lesion in low-risk asymptomatic community population. Through study completion, an average of 1 year
Enrollment 11000
Condition
Intervention

Intervention Type: Diagnostic Test

Intervention Name: Stool-based SDC2 DNA methylation test

Description: A diagnostic device measuring syndecan 2(SDC2) methylation status in stool DNA to detect colorectal cancer

Other Name: COLOSAFE(or named Chang An Xin)

Intervention Type: Diagnostic Test

Intervention Name: quantitative Fecal immunochemical test

Description: A diagnostic device using immunoturbidimetric methods to measure fecal hemoglobin concentration

Other Name: OC-Sensor

Eligibility

Sampling Method:

Non-Probability Sample

Criteria:

Inclusion Criteria: 1. Asymptomatic individual (no alarm features predicting colorectal cancer including hematochezia, melena, anemia of unknown cause, weight loss, abdominal mass, a positive result of digital rectal examination) 2. Age between 45 to 75 years old, the gender is not limited 3. Willing to participate and sign informed consent Exclusion Criteria: 1. Patients with contraindications for bowel preparation or colonoscopy 2. Patients with known colorectal adenoma or serrated lesions (not include hyperplastic, inflammatory, or hamartomatous polyp, no matter remove) 3. History of colonoscopy within 5 years 4. Patients with inflammatory bowel disease 5. History of CRC and patients clinically highly suspected with colorectal cancer 6. History of hereditary CRC syndrome (including polyposis) 7. Patients taking anticoagulants such as aspirin and warfarin within 7 days, or who have coagulopathy 8. Pregnancy, or severe organ insufficiency (heart, lung, or kidney et al) 9. Patients do not agree to undergo colonoscopy after initial evaluation Elimination Criteria: 1. Unable to undergo colonoscopy or failed to complete the colonoscopy 2. Unable to get FIT or sDNA sample 3. Invalid FIT or sDNA test

Gender:

All

Minimum Age:

45 Years

Maximum Age:

75 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Zhaoshen Li, MD Principal Investigator Changhai Hospital, Navy/Second Military Medical University
Overall Contact

Last Name: Zhaoshen Li, MD

Phone: +86-21-25070552

Email: [email protected]

Location
Facility: Status: Contact: Changhai Hospital Shengbing Zhao, Doctor 15301652570 [email protected]
Location Countries

China

Verification Date

2021-09-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Changhai Hospital

Investigator Full Name: Zhaoshen Li

Investigator Title: MD,Director, Head of Department of Gastroenterology and Digestive Endoscopy Center, Principal Investigator, Clinical Professor

Keywords
Has Expanded Access No
Condition Browse
Patient Data Undecided
Study Design Info

Observational Model: Case-Only

Time Perspective: Cross-Sectional

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