Endoscopic Surveillance in Patients With Serrated Polyposis Syndrome and Low-risk of Advanced Neoplasia.

Colorectal cancer (CRC) is the most frequent neoplasm in developed countries considering both sexes and is the second in terms of cancer mortality. The incidence of the CRC is increasing in all developed countries. Detection of precancerous lesions (colon polyps) or malignant lesions (adenocarcinoma) in early stages in screening programs improves the prognosis and decreases the mortality of these patients. Serrated polyposis syndrome (SPS) is the most common colorectal polyposis syndrome and is characterized by the combination of large and/or numerous serrated lesions (SL) throughout the colorectum. There are three different types of SLs described: hyperplastic polyps (HP), sessile serrated lesions (SSL) and traditional serrated adenomas (TSA).

In 2010 the world health organization (WHO) defined the clinical criteria for the SPS diagnosis: criteria I, any patient with ≥ 5 serrated lesions proximal to the sigma, two of them> 1 cm in size; criteria II, any first degree relative of a SPS patient with at least one serrated lesion; criteria II, any patient with ≥20 serrated lesions throughout the colon. This criteria were reviewed in 2019 and criteria II was eliminated. The new criteria are: criteria 1, any patient with ≥ 5 SL proximal to the rectum, all ≥5 mm in size, with at least 2 lesions ≥10 mm in size; criteria 2, any patient with >20 SL of any size distributed throughout the colon, with ≥5 lesions proximal to the rectum.

In recent years, a new pathway in the development of colorectal adenocarcinoma have been described, the "serrated pathway". It is associated with mutations in BRAF and KRAS genes, the existence of hypermethylation in the promoter regions "CpG island" and microsatellite instability phenotype caused by methylation of the MLH-1 gene. This new pathway has a faster progression from the serrated polyp to the CRC in comparison with the classic "adenoma-carcinoma" pathway, hence the importance of detecting and removing these lesions in patients with SPS.

CRC prevalence in patients diagnosed with SPS is 15-35%, according to different studies, and the probability at 5 years of developing a CRC is around 1.3-1.9%. During surveillance, the incidence of advanced neoplasia (advanced adenoma or advanced serrated lesions) at 3 years is 13% for adenomas and 42 for serrated lesions. Risk factors for developing CRC and advanced neoplasia have been described in several studies. One of these factors is the SPS criteria 2, which has been demonstrated as a low risk of CRC and advanced neoplasia during surveillance of SPS patients. Detecting more than two sessile serrated lesions proximal to the spleenic flexure, one sessile serrated lesion with high grade of dysplasia and the detection of advanced neoplasia in previous colonoscopies, are all risk factors of developing advanced neoplasia during surveillance. A recent multicentre prospective study established SPS patient surveillance according to lesions detected at last colonoscopy. Individuals with at least one advanced adenoma, an advanced serrated lesion or more than 5 relevant lesions (sessile serrated lesions, adenomas of any size or hyperplastic polyps more than 5 mm) were followed at one year. Patients with no lesions mentioned before were followed at 2 years with colonoscopy. Advanced neoplasia incidence in 2 years recommendation surveillance was 15.6% compared with 24.4% in the 1 year recommendation surveillance. CRC cumulative 5 years incidence was 1.3%. Regarding SPS type, the 5 years advanced neoplasia incidence was lower for patients with SPS criteria III of 2010 (26%) than for patients diagnosed with criteria I (53%) or criteria I and III (59%). In this study patients starting their surveillance with clearing phase achieved (clear colon of all polyps ≥5mm and all polyps with the optical aspect of adenoma, TSA or SSL) were at low risk of advanced neoplasia than patients without this phase achieve prior to study inclusion (HR: 0.64; p<0.047).

With all the above described, the investigators can define a SPS patient with low risk of advanced neoplasia during surveillance: those patients with SPS criteria 2, with clearing phase achieved and without any advanced lesion or less than 5 relevant lesions at last colonoscopy.