Clinical and Endoscopic Characterization of Patients With Multiple Colorectal Adenomas: A Multicenter Study in Spain (ESPAPOLYP Study)

HYPOTHESIS

Better characterization of patients with MAC (multiple adenomatous colorectal polyps) could help identify predictive factors of germline pathogenic variants.

Identifying predictive factors of germline pathogenic variants would help optimize and standardize selection criteria for MAC patients to undergo genetic panel testing.

The identification of extra-colonic manifestations in these patients would help implement relevant screening strategies.

Studying the incidence of advanced neoplasia in surveillance colonoscopies in MAC patients would help optimize the intervals for endoscopic surveillance.

Understanding the risk of developing CRC and/or MAC in first-degree relatives of MAC patients without known germline pathogenic variants would allow the establishment of specific colorectal neoplasia screening in this population.

The use of the FIT (fecal immunochemical test) in CRC and/or MAC screening in first-degree relatives (FDR) of MAC patients could be useful by reducing the rate of unnecessary colonoscopies.

OBJECTIVES

The project is subdivided into the following four subprojects:

SUBPROJECT 1: GENPOLYP PROTOCOL

Objectives:

To assess adherence to clinical practice guidelines for requesting genetic testing.

To determine which clinical practice guideline is most used for requesting genetic testing.

To establish the prevalence of germline pathogenic mutations in patients with MAP (multiple adenomatous polyps).

To evaluate predictive factors of germline pathogenic mutations in patients with MAP.

SUBPROJECT 2: RE-SURVPOLYP

Objectives:

Clinical characterization of the cohort. To evaluate the prevalence of CRC and advanced neoplasia in patients with MAC. To evaluate the prevalence of gastroduodenal manifestations. To evaluate the prevalence of non-gastrointestinal manifestations. To determine the need for colorectal surgery in MAC patients. To assess the prevalence of CRC and advanced neoplasia in post-surgical surveillance.

SUBPROJECT 3: PRO-SURVPOLYP

Objectives:

To establish the post-polypectomy surveillance schedule based on the AEG/SEMFYC guidelines.

To assess the incidence of advanced neoplasia and CRC at 3, 5, and 10 years. To evaluate predictive factors of advanced neoplasia in surveillance colonoscopies.

To assess CRC mortality at 5 and 10 years. To assess the incidence of fundic gland polyps, gastric adenomas, duodenal adenomas, and ampullary adenomas at 3, 5, and 10 years.

To assess the incidence of ampullary and duodenal adenocarcinoma at 3, 5, and 10 years.

To evaluate the prevalence of H. pylori. To establish screening indications for gastroduodenal lesions, appropriate surveillance intervals, and the endoscopic technique to be used.

SUBPROJECT 4: FAMPOLYP Subproject 4.1: RE-FAMPOLYP

Objective:

To describe the clinicopathological characteristics of the cohort. To evaluate the prevalence of MAC in first-degree relatives (FDRs) of patients with multiple colorectal adenomas.

To evaluate the prevalence of CRC in FDRs of MAC patients. To evaluate the prevalence of variants of uncertain significance (VUS) coinciding between FDRs of patients with multiple colorectal adenomas for whom a multigene panel was requested.

Subproject 4.2: PRO-FAMPOLYP

Objectives:

To evaluate the incidence of CRC and advanced neoplasia in FDRs of patients with MAC under endoscopic surveillance at 5 years.

To assess the incidence of MAC diagnosis in FDRs of patients with MAC under endoscopic surveillance at 5 years.

To evaluate the diagnostic accuracy of the FIT test for CRC screening in FDRs of MAC patients.

METHODOLOGY AND WORK PLAN

SUBPROJECT 1: GENPOLYP PROTOCOL Design: Prospective, multicenter, observational study.

Methodology:

Patient Selection:

In this protocol, all patients who are detected with ≥10 adenomas in consecutive colonoscopies or a single colonoscopy and/or surgical specimen (if they have undergone colorectal surgery) who have not previously undergone germline genetic testing via a multigene panel will be prospectively included. Patients from families with a previously identified germline pathogenic mutation, those with inflammatory bowel disease (IBD), and those with low performance status (ECOG 3-4) will be excluded. Patients who, due to cognitive decline, cannot make decisions may be included if their legal guardian authorizes their inclusion.

In these patients, a multigene panel test will be requested, which must include the study of at least the following genes: MLH1, MSH2, PMS2, MSH6, EPCAM, APC, MUTYH, BMPR1A, PTEN, STK11, SMAD4, POLD, POLE, NTHL1, RNF43, BRCA1, BRCA2, GREM1.