Polyprev: Study to Compare Fecal Immunochemical Test With Endoscopic Surveillance After Advanced Adenoma Resection in Fecal Immunochemical Test Colorectal Cancer Screening Programs.

Study Overview
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Brief Summary
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Colorectal cancer (CRC) screening programs have been implemented to reduce the burden of the disease. When an advanced colonic lesions is detected, it is recommended to perform endoscopic surveillance with different intervals between explorations. Although the reduction in CRC incidence, endoscopic surveillance is producing a considerable increase in the number of colonoscopies. However, participation in CRC screening programs based on the fecal immunochemical test (FIT) could be a non inferior alternative to endoscopic surveillance. Based on this hypothesis, the research group have designed a randomized clinical trial within the population CRC screening programs to compare FIT surveillance to endoscopic surveillance in patients with advanced lesions resected.

Detailed Description
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Colorectal cancer (CRC) is one of the most common malignancies in western countries. CRC screening programs have been implemented in order to reduce the burden of the disease. Screening programs in Spain are based on the biennial detection of fecal hemoglobin with a fecal immunochemical test (FIT) and a diagnostic colonoscopy if positive. The detection of at least one advanced adenoma or serrated lesion defines a high risk situation for metachronous CRC. This group of patients is recommended to perform endoscopic surveillance with different intervals between explorations. Endoscopic surveillance reduces mortality only 1.7% and increases the number of colonoscopies by 62% with an additional cost of € 68,000 for an increase of 0.9 years of life. Moreover, colonoscopy is a procedure associated with potentially serious side effects. A recently British study shows that with a cut-off of 10 µg/g, FIT has a higher sensitivity and specificity for CRC with a significant cost reduction compared to colonoscopy surveillance. Additionally, most of the population prefers non-invasive faecal tests rather than colonoscopy. Based on this evidence, the research group have designed a multicenter, randomized clinical trial to compare the 10 year CRC incidence after resection of advanced colonic lesions detected within CRC screening programs between endoscopic surveillance and participation in CRC screening programs based on FIT. Apart from this purpose, the investigators will also assess the values and preferences regarding surveillance and risk of CRC. Further, the research group will evaluate the relationship between Mediterranean diet and physical activity with the detection of advanced adenomas and CRC.

Official Title
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Polyprev Study: Randomized, Multicenter, Controlled Trial Comparing Fecal Immunochemical Test With Endoscopic Surveillance After Advanced Adenoma Resection in Fecal Immunochemical Test Colorectal Cancer Screening Programs.

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Diagnostic Test: Annual FIT
* Procedure: Endoscopic surveillance.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals aged 50 to 65 years. Individuals with at least one advanced adenoma (tubulovillous or villous histology, high grade dysplasia or ≥ 10mm), and / or at least three non-advanced adenomas detected and resected completely within the population-based CRC screening program. Exclusion Criteria: Personal history of CRC. Colonic lesion ≥10mm resected without histological diagnosis. More than 10 adenomas in baseline colonoscopy. Serrated polyposis syndrome. Two or more first-degree relatives with CRC. Hereditary predisposition to CRC. Relevant comorbidity with life expectancy inferior to 5 years. Colonoscopy with incomplete mucosal examination. Incomplete resection of baseline lesions. Non-acceptance after reading the informed consent.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be identified in population CRC secreening programs of Galicia, the Basque Country, the Region of Valencia and Murcia. We will considered individuals aged 50 to 65 years with at least one advanced adenoma (tubulovillous or villous histology, high grade dysplasia or ≥ 10mm), and / or at least three non-advanced adenomas detected and resected completely within the population-based CRC screening program. Patients will be randomly allocated to perform an annual FIT and colonoscopy if fecal hemoglobin concentration is ≥10µg/g, or to perform endoscopic surveillance. Patients will be also stratified into two groups: ≥5 adenomas or an adenoma ≥20mm and the rest of patients. Patients will be followed for a period of 10 years.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br>Annual FIT surveillance | Diagnostic Test: Annual FIT<br>* Patients will be offered an annual FIT and colonoscopy will be performed if fecal hemoglobin concentration is ≥10µg / g of feces. After performing a colonoscopy the FIT will be sent to the patient: After one year if the unscheduled colonoscopy has been incomplete or a lesion requiring endoscopic surveillance has been completely resected. After five years if the colonoscopy has evaluated the entire mucosa, it is normal or with lesions that do not require endoscopic surveillance (1-2 non-advanced adenomas).<br>|
| Active Comparator: Group II<br>Endoscopic surveillance | Procedure: Endoscopic surveillance.<br>* First surveillance colonoscopy will be performed in three-year time. If an advanced adenoma or at least three non-advanced adenomas are detected, colonoscopy will be repeated after 3 years. In contrast, if colonoscopy is normal or 1-2 non-advanced adenomas are detected, colonoscopy will be repeated after 5 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of invasive CRC | It is the main outcome of the study. Invasive CRC is defined as colonic adenocarcinoma that invades the submucosa. Adenocarcinomas in situ and intramucosal carcinomas will not be considered as invasive CRC. | 10 years | 
| Rate of interval CRC | Interval CRC is defined as the CRC detected between two organized surveillance (FIT or colonoscopy). | 10 years | 
| Mortality | The deaths and their cause will be collected: associated with CRC, associated with adverse effects of screening or unrelated. | 10 years | 
| Rate of advanced colonic lesions | Advanced colonic lesions will be defined as advanced adenomas (at least 10mm, hairy histology or high grade dysplasia) or advanced serrated lesions (at least 10mm or with dysplasia). | 10 years | 
| Frequency of participation in the surveillance strategy | According to the methodology of the information systems of the screening programs, three categories will be defined: non-participation, irregular participation, regular participation. | 10 years | 
| Adverse effects | Adverse effects associated with surveillance are defined as complications that require hospitalization. Those related to the surgical treatment of benign colonic lesions will be included as adverse effects. | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRC, adenoma and advanced serrated lesions at three years | Detection of CRC, adenoma and advanced serrated lesion will be collected at 3 years of follow-up. | 3 years | 
| Physical activity | We will use the International Physical Activity. Questionnaire (IPAQ) to mesure physical activity. | 3 years | 
| Mediterranean lifestyle | We will use the Mediterranean Lifestyle index (MEDLIFE) to measure overall adherence to the Mediterranean lifestyle. | 3 years | 
| Preferences of the subjects | We will use a survey with vignette questions to evaluate the values and preferences of the subjects regarding surveillance. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Screening program, Endoscopic surveillance, Fecal immunochemical test, Mediterranean diet, Physical activity