SSAT - Metachronous Colorectal Cancer Risk Following Surgery for First Rectal Cancer in Mismatch Repair Gene Mutation Carriers

Metachronous Colorectal Cancer Risk Following Surgery for First Rectal Cancer in Mismatch Repair Gene Mutation Carriers
Aung Ko Win^*¹, Susan Parry^2,3, Bryan Parry⁴, Matthew F. Kalady⁵, Finlay a. Macrae⁶, Noralane M. Lindor⁷, Robert W. Haile⁸, Polly a. Newcomb⁹, LoïC LE Marchand¹⁰, Steven Gallinger^11,12, John Hopper¹, Mark a. Jenkins¹
¹Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Carlton, VIC, Australia; ²New Zealand Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand; ³Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand; ⁴Colorectal Surgical Unit, Auckland City Hospital, Auckland, New Zealand; ⁵Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH; ⁶Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, VIC, Australia; ⁷Department of Medical Genetics, Mayo Clinic, Rochester, MN; ⁸Department of Preventive Medicine, University of Southern California, Los Angeles, CA; ⁹Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA; ¹⁰University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI; ¹¹Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; ¹²Cancer Care Ontario, Toronto, ON, Canada

Background: Metachronous colorectal cancer risk for Lynch syndrome patients with primary colon cancer is high and total colectomy is the preferred option. However if the index primary cancer is in the rectum, management advice is complicated by considerations of worsening bowel function or stoma formation. To aid surgical decision-making, we estimated the risk of metachronous colon cancer for Lynch syndrome patients who underwent either anterior resection or abdominoperineal resection for primary rectal cancer.

Methods: This retrospective cohort study comprised 79 MMR gene mutation carriers (18 MLH1, 55 MSH2, 4 MSH6 and 2 PMS2) from the Colon Cancer Family Registry who had a surgical resection for their first primary rectal cancer. Age-dependent cumulative risks of metachronous colon cancer were calculated using the Kaplan-Meier method. Risk factors for metachronous colon cancer were assessed using a Cox proportional hazards regression.

Results: During 866 person-years of observation (median 9 years; range 1-32 years) since diagnosis of first rectal cancer, a total of 21 (27%) carriers were diagnosed with metachronous colon cancer (incidence 24.2; 95% CI 15.8-37.2 per 1000 person-years). Incidence for carriers who had an anterior resection (26.8; 95% CI 15.5-46.1 per 1000 person-years) was not different from that for carriers who had an abdominoperineal resection (21.0; 95% CI 10.5-42.1 per 1000 person-years) (P=0.1). Cumulative risk of metachronous colon cancer was 19% (95% CI 9-31%) at 10 years, 47% (95% CI 31-68%) at 20 years and 69% (95% CI 45-89%) at 30 years after surgical resection. There was no difference in the frequency of surveillance colonoscopy between the two types of surgery (one colonoscopy per 1.1 (95% CI 0.9-1.2) years after anterior resection vs. one colonoscopy per 1.4 (95% CI 1.0-1.8) years after abdominoperineal resection).

Conclusions: For carriers of MMR gene mutations diagnosed with rectal cancer, the metachronous colon cancer risk is substantial and mirrors that seen for carriers who have undergone segmental resection for primary colon cancer, despite the majority continuing to receive frequent surveillance colonoscopy. Whereas total colectomy for primary colon cancer in mutation carriers is appropriate, for primary rectal cases this strategy has major implications for continence and need for stoma. Nevertheless, given the high metachronous risk, this procedure needs serious consideration especially for younger patients.

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