Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery

Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, Baron JA, Giles GG, Leggett BA, Winship I, Lipton L, Young GP, Young JP, Lodge CJ, Southey MC, Newcomb PA, Le Marchand L, Haile RW, Lindor NM, Gallinger S, Hopper JL, Jenkins MA (2011) Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut 60:950-957

BACKGROUND: Surgical management of colon cancer for patients with Lynch syndrome who carry a mismatch repair (MMR) gene mutation is controversial. The decision to remove more or less of the colon involves the consideration of a relatively high risk of metachronous colorectal cancer (CRC) with the impact of more extensive surgery. OBJECTIVE: To estimate and compare the risks of metachronous CRC for patients with Lynch syndrome undergoing either segmental or extensive (subtotal or total) resection for first colon cancer. DESIGN: Risk of metachronous CRC was estimated for 382 MMR gene mutation carriers (172 MLH1, 167 MSH2, 23 MSH6 and 20 PMS2) from the Colon Cancer Family Registry, who had surgery for their first colon cancer, using retrospective cohort analysis. Age-dependent cumulative risks of metachronous CRC were calculated using the Kaplan-Meier method. Risk factors for metachronous CRC were assessed by a Cox proportional hazards regression. RESULTS: None of 50 subjects who had extensive colectomy was diagnosed with metachronous CRC (incidence rate 0.0; 95% CI 0.0 to 7.2 per 1000 person-years). Of 332 subjects who had segmental resections, 74 (22%) were diagnosed with metachronous CRC (incidence rate 23.6; 95% CI 18.8 to 29.7 per 1000 person-years). For those who had segmental resections, incidence was statistically higher than for those who had extensive surgery (P <0.001). cumulative="" risk="" of="" metachronous="" crc="" was="" 16%="" (95%="" ci="" 10%="" to="" 25%)="" at="" 10="" years,="" 41%="" (95%="" ci="" 30%="" to="" 52%)="" at="" 20="" years="" and="" 62%="" (95%="" ci="" 50%="" to="" 77%)="" at="" 30="" years="" after="" segmental="" colectomy.="" risk="" of="" metachronous="" crc="" reduced="" by="" 31%="" (95%="" ci="" 12%="" to="" 46%;="" p="0.002)" for="" every="" 10="" cm="" of="" bowel="" removed.="" conclusions:="" patients="" with="" lynch="" syndrome="" with="" first="" colon="" cancer="" treated="" with="" more="" extensive="" colonic="" resection="" have="" a="" lower="" risk="" of="" metachronous="" crc="" than="" those="" receiving="" less="" extensive="" surgery.="" this="" finding="" will="" better="" inform="" decision-making="" about="" the="" extent="" of="" primary="" surgical="">