Serrated Polyposis Syndrome: A Narrative Review from Clinical Recognition to Risk-Adapted Cancer Prevention.

Serrated polyposis syndrome (SPS) is a clinically defined colorectal polyposis syndrome characterized by multiple and/or large serrated lesions and an increased risk of colorectal cancer (CRC). Its diagnosis remains challenging because it depends on cumulative endoscopic and histopathological findings rather than a single germline marker, and it remains under-recognized in routine practice. The biological basis of SPS is heterogeneous: serrated tumorigenesis commonly involves BRAF or KRAS activation, CpG island methylation, and MLH1 silencing, yet most cases are not explained by classic Mendelian inheritance and SPS-associated CRC may arise through serrated or conventional adenoma-carcinoma pathways. This narrative review integrates current evidence on clinical recognition, WHO diagnostic criteria, cancer risk, biological heterogeneity, endoscopic clearance, surveillance, surgery, and family screening. After high-quality clearance, surveillance can be adapted dynamically using the most recent clinical, endoscopic, and pathological findings, including polyp burden, advanced serrated lesions, dysplasia, advanced adenomas, prior CRC, and completeness of resection. At present, these conventional variables and guideline-based intervals constitute current practice; germline, epigenetic, microbiome, metabolomic, and other non-invasive biomarkers remain investigational and should not determine routine surveillance. A phase-based approach combining cumulative diagnosis, effective clearance, risk-adapted 1- or 2-year surveillance, selective surgery, and screening of first-degree relatives provides a pragmatic framework for CRC prevention.