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

Official title

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.

Overview

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

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.

Interventions

• Diagnostic test Annual FIT
  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-adva
• Procedure Endoscopic surveillance.
  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.

Primary outcome measures

• Rate of invasive CRC [Time frame: 10 years]
• Rate of interval CRC [Time frame: 10 years]
• Mortality [Time frame: 10 years]
• Rate of advanced colonic lesions [Time frame: 10 years]
• Frequency of participation in the surveillance strategy [Time frame: 10 years]
• Adverse effects [Time frame: 10 years]

Secondary outcome measures (4)

• CRC, adenoma and advanced serrated lesions at three years [Time frame: 3 years]
• Physical activity [Time frame: 3 years]
• Mediterranean lifestyle [Time frame: 3 years]
• Preferences of the subjects [Time frame: 2 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Screening

Study locations

Spain · 1 center

• Complexo Hospitalario Universitario de Ourense — Ourense

Publications

• Holleczek B, Rossi S, Domenic A, Innos K, Minicozzi P, Francisci S, Hackl M, Eisemann N, Brenner H; EUROCARE-5 Working Group:. On-going improvement and persistent differences in the survival for patients with colon and rectum cancer across Europe 1999-2007 - Results from the EUROCARE-5 study. Eur J Cancer. 2015 Oct;51(15):2158-2168. doi: 10.1016/j.ejca.2015.07.024. Epub 2015 Sep 26. PMID 26421819
• Atkin WS, Valori R, Kuipers EJ, Hoff G, Senore C, Segnan N, Jover R, Schmiegel W, Lambert R, Pox C; International Agency for Research on Cancer. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Colonoscopic surveillance following adenoma removal. Endoscopy. 2012 Sep;44 Suppl 3:SE151-63. doi: 10.1055/s-0032-1309821. Epub 2012 Sep 25. PMID 23012119
• Bretthauer M, Loberg M, Kalager M. Long-term colorectal-cancer mortality after adenoma removal. N Engl J Med. 2014 Nov 20;371(21):2036-7. doi: 10.1056/NEJMc1411954. No abstract available. PMID 25409378
• Zauber AG, Winawer SJ, O'Brien MJ, Lansdorp-Vogelaar I, van Ballegooijen M, Hankey BF, Shi W, Bond JH, Schapiro M, Panish JF, Stewart ET, Waye JD. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012 Feb 23;366(8):687-96. doi: 10.1056/NEJMoa1100370. PMID 22356322
• Martinez ME, Baron JA, Lieberman DA, Schatzkin A, Lanza E, Winawer SJ, Zauber AG, Jiang R, Ahnen DJ, Bond JH, Church TR, Robertson DJ, Smith-Warner SA, Jacobs ET, Alberts DS, Greenberg ER. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology. 2009 Mar;136(3):832-41. doi: 10.1053/j.gastro.2008.12.007. Epub 2008 Dec 9. PMID 19171141
• Hassan C, Quintero E, Dumonceau JM, Regula J, Brandao C, Chaussade S, Dekker E, Dinis-Ribeiro M, Ferlitsch M, Gimeno-Garcia A, Hazewinkel Y, Jover R, Kalager M, Loberg M, Pox C, Rembacken B, Lieberman D; European Society of Gastrointestinal Endoscopy. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2013 Oct;45(10):842-51. doi: PMID 24030244
• Cubiella J, Carballo F, Portillo I, Cruzado Quevedo J, Salas D, Binefa G, Mila N, Hernandez C, Andreu M, Teran A, Arana-Arri E, Ono A, Valverde MJ, Bujanda L, Hernandez V, Morillas JD, Jover R, Castells A. Incidence of advanced neoplasia during surveillance in high- and intermediate-risk groups of the European colorectal cancer screening guidelines. Endoscopy. 2016 Nov;48(11):995-1002. doi: 10.105 PMID 27485482
• Mangas-Sanjuan C, Jover R, Cubiella J, Marzo-Castillejo M, Balaguer F, Bessa X, Bujanda L, Bustamante M, Castells A, Diaz-Tasende J, Diez-Redondo P, Herraiz M, Mascort-Roca JJ, Pellise M, Quintero E; Grupo de Cribado del Cancer Colorrectal de la Sociedad Espanola de Epidemiologia. Endoscopic surveillance after colonic polyps and colorrectal cancer resection. 2018 update. Gastroenterol Hepatol. 201 PMID 30621911

Identifiers

NCT: NCT04967183 · POLYPREV

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗