Risk of Metachronous Colon Cancer Following Surgery for Rectal Cancer in Mismatch Repair Gene Mutation Carriers
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Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer.
This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer. Cumulative risks of metachronous colon cancer were calculated using the Kaplan–Meier method.
During median 9 years (range 1–32 years) of observation since the first diagnosis of rectal cancer, 21 carriers (27 %) were diagnosed with metachronous colon cancer (incidence 24.25, 95 % confidence interval [CI] 15.81–37.19 per 1,000 person-years). 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. The frequency of surveillance colonoscopy was 1 colonoscopy per 1.16 years (95 % CI 1.01–1.31 years). The AJCC stages of the metachronous cancers, where available, were 72 % stage I, 22 % stage II, and 6 % stage III.
Given the high metachronous colon cancer risk for MMR gene mutation carriers diagnosed with an index rectal cancer, proctocolectomy may need to be considered.
KeywordsRectal Cancer Lynch Syndrome Multiplex Ligation Dependent Probe Amplification Subtotal Colectomy Surveillance Colonoscopy
The authors thank all study participants of the Colon Cancer Family Registry and staff for their contributions to this project.
The authors have no conflict of interest to declare with respect to this manuscript.
This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. Collaborating centers include Australasian Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01 CA074799) [USC], Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). AKW is supported by the Picchi Brothers Foundation Cancer Council Victoria Cancer Research Scholarship, Australia. MAJ is a Senior Research Fellow and JLH is an Australia Fellow of the National Health and Medical Research Council, Australia.
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