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

Abstract

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. 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. 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. 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.