Risk of Metachronous Colorectal Cancer after Segmental or Extended Resection in Patients with Lynch Syndrome

BACKGROUND: The recommendation for patients with Lynch syndrome (LS) to undergo extended colectomy at colorectal cancer (CRC) diagnosis is increasingly controversial due to associated long-term morbidity, no benefit in overall survival, and recent advances in immunotherapy. STUDY DESIGN: A prospective institutional database was queried for patients with LS diagnosed with CRC between 1969 and 2024, and rates of metachronous CRC and 10-year overall survival were analyzed. RESULTS: Metachronous CRC, with a median of 13 (interquartile range 5 to 20) years between diagnoses, occurred in 88 of 450 patients (20%): 83 of 350 patients (24%) who underwent segmental resection, 2 of 40 patients (5%) who underwent extended resection, and 3 of 60 patients (5%) who did not undergo surgery. Metachronous CRC was more common in patients with variants in high-risk ( MLH1 , MSH2 ) vs low-risk ( MSH6 , PMS2 ) genes: 80 of 326 patients (25%) vs 8 of 124 patients (6%) (p < 0.001). Extended resection was associated with a lower rate of metachronous CRC compared with segmental resection in patients with high-risk variants (2 [6%] of 34 vs 75 [30%] of 252; p = 0.006) but not in patients with low-risk variants (0 of 6 vs 8 [8%] of 98; p = 1.00). Ten-year overall survival was 90% (95% CI 86% to 93%) for the full cohort (median follow-up, 7.0 years), 89% (95% CI 85% to 93%) after segmental resection, and 96% (95% CI 88% to 100%) after extended resection. CONCLUSIONS: For CRC patients with variants in high-risk LS genes, extended resection can significantly reduce the risk of metachronous CRC but does not lengthen overall survival. Segmental resection with close endoscopic surveillance can be a reasonable alternative, given the opportunity for repeat surgery or immune checkpoint blockade.