Contemporary Surgical Management of Colorectal Cancer in Lynch Syndrome: Considering the Implications of Known Genotype.

Abstract

Background: Lynch syndrome (LS) is an autosomal dominant disorder caused by germline mutations in mismatch repair (MMR) genes, accounting for 1%-3% of all colorectal cancer (CRC) diagnoses. It is associated with an elevated lifetime CRC risk of 30%-80% and predisposes individuals to various extra-colonic malignancies. Advances in genetic profiling have refined our understanding of LS, offering opportunities to tailor surgical and surveillance strategies.

Summary: The surgical management of LS is shifting from a uniform, aggressive approach to more nuanced strategies guided by patient-specific factors, including age, tumor characteristics, and genetic variants. While extended resections reduce metachronous CRC risk, they may not significantly improve survival compared to segmental resections and can negatively affect quality of life. Enhanced surveillance and emerging therapies, such as chemoprophylaxis and immunotherapy, are further reshaping treatment paradigms.

Key message: Surgical management of LS must remain patient-centered, integrating functional outcomes, genetic risk, and individual circumstances. Genetic-variant-specific recommendations, coupled with personalized surveillance strategies, are essential to optimizing care without compromising survival or quality of life.