Immunotherapy and surgical decision-making in Lynch syndrome-associated colorectal cancer: Implications for personalized management and guideline revision.

Lynch syndrome (LS), the most common hereditary colorectal cancer (CRC) syndrome, confers a lifetime CRC risk of 40-80%. Historically, most guidelines have recommended subtotal colectomy at diagnosis to reduce metachronous cancer risk. However, the immune checkpoint inhibitors (ICIs) have fundamentally transformed the therapeutic landscape of microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) CRC. Recent clinical trials have shown unprecedented pathological complete response (pCR) ranging from 60 to 100% in MSI-H/dMMR CRC treated with ICIs. Multiple studies, including the landmark NICHE trials and case reports of LS patients with metastatic disease achieving pCR after immunotherapy challenge the necessity of extensive prophylactic surgery. This narrative review comprehensively synthesizes evidence from neoadjuvant immunotherapy trials, metastatic disease outcomes, contemporary metachronous risk studies, and current guideline recommendations. While acknowledging constraints such as limited cohort, long term follow-up, and substantial variation in global access to immunotherapy, the convergence of remarkable immunotherapy efficacy and lack of survival benefit from extended colectomy warrants reassessment of surgical management strategies. We propose that international guidelines reassess their recommendations to reflect this evolving therapeutic landscape by shifting from routine subtotal colectomy recommendations toward an individualized, biology-informed recommendation.