EP552 - Mutation-Specific Decision Model for Segmental Versus Total Abdominal Colectomy in Hereditary Nonpolyposis Colorectal Cancer

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Purpose/Background: Patients with Hereditary Nonpolyposis Colorectal Cancer (HNPCC) are at increased risk of developing metachronous cancers, although risk varies considerably among different mismatch repair (MMR) mutations. When considering surgical options for colon cancer, total abdominal colectomy (TAC) offers a decreased risk of metachronous occurrences but with decreased quality of life compared to a segmental resection (SEG). Our study provides a state-transition (Markov) model that compares both survival and quality-adjusted life years (QALYs) for SEG versus TAC strategies, stratified by MMR mutation.

Methods/Interventions: We constructed a Markov model using current literature and data sources simulating survival and colorectal metachronous occurrences among patients with MLH1, MSH2, or MSH6 mutations. PMS2 mutations were excluded due to the limited availability of data on metachronous cancers. We simulated cohorts of 100,000 patients to undergo one of two strategies: (1) initial SEG, with subsequent TAC for colon metachronous cancer and/or ileal pouch-anal anastomosis (IPAA) for rectal metachronous cancer; or (2) initial TAC, with subsequent IPAA for rectal metachronous cancer. We measured both mean survival and QALYs based on utility states related to each surgical procedure (0.99 SEG, 0.95 TAC, and 0.89 IPAA), with a discount rate of 2%. Simulations were run for varying ages at initial diagnosis, and sensitivity analyses were conducted to determine how model assumptions affected QALYs and survival.

Results/Outcomes: Among young patients (age 25 at diagnosis), TAC offered less than 1 year of increased mean survival when compared to SEG across all mutations (MLH1: 0.8 years, MSH2: 0.9 years, and MSH6: 0.3 years). Patients with an MSH6 mutation had slightly better survival when diagnosed at age 60-70 and undergoing SEG compared to TAC. Patients with MLH1 and MSH2 mutations did not show a similar improved survival until diagnosis after age 70. SEG offered a small increase in QALYs compared to TAC across all diagnosis ages but was highest for patients with the MSH6 mutation (0.9 vs. MLH1: 0.6 vs. MSH2: 0.4 for diagnosis at age 25). Patients with MSH6 mutations had higher QALYS with SEG compared to TAC compared to MLH1 and MSH2, but this decreased with increasing age (Figure 1). In a sensitivity analysis varying the TAC utility state from 0.90 to 0.99, lower TAC utility states resulted in greater differences in mean QALYs offered by SEG versus TAC across all ages with the largest difference in MSH6 patients.

Conclusion/Discussion: Among patients with colon cancer and HNPCC, SEG and TAC offer similar survival and QALY outcomes. With decreased risk of metachronous cancers, patients with MSH6 mutations have higher QALYs with SEG over TAC and lower survival benefits from TAC over SEG across different ages of diagnosis compared to patients with MLH1 and MSH2 mutations. These differences though are small. Therefore, SEG may be preferable to TAC for patients with MSH6 mutations at all ages of diagnosis, but less so for MLH1 or MSH2 mutations, particularly at younger ages at diagnosis. Decision making for SEG or TAC in patients with HNPCC should be individualized and this study shows that the mutation-specific differences in survival and QALYs are small.