Catherine G Tran1, Paolo Goffredo2, Sarah L Mott3, Alexander Hart1, Y Nancy You4, Jean-Nicolas Vauthey4, Ronald J Weigel1, Imran Hassan5. 1. Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA. 2. Division of Colon and Rectal Surgery, University of Minnesota, Minneapolis, MN. 3. Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA. 4. Department of Colorectal Surgery, University of Texas MD Anderson Cancer Center, Houston, TX. 5. Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA. Electronic address: imran-hassan@uiowa.edu.
Abstract
BACKGROUND: KRAS mutations, microsatellite instability, and tumor location have been found to be significant prognostic factors in colorectal cancer. The interaction between these variables and its effect on overall survival in nonmetastatic colon cancer has not been well elucidated. METHODS: The National Cancer Database (2010-2016) was queried for patients with stage I-III colon cancer and known microsatellite instability and KRAS status undergoing curative resection. RESULTS: A total of 5,292 patients were identified: 60.4% had right-sided cancers, 36.4% had KRAS mutations, and 15.6% had microsatellite instability. Right-sided tumors were more likely to have microsatellite instability and KRAS mutations compared to left-sided tumors. On univariable analysis, KRAS mutations and microsatellite instability status were not associated with differences in survival, whereas right-sided cancers had worse overall survival compared to left-sided cancers (hazard ratio 1.32, 95% confidence interval: 1.18-1.47). On multivariable analysis, right-sided location, KRAS mutations, and microsatellite instability were not independent prognostic factors. However, a significant interaction between laterality and KRAS status was observed. In patients with mutated KRAS cancers, left-sided tumors were at increased risk of death compared to right-sided tumors (hazard ratio: 1.30, 95% confidence interval: 1.03-1.63), whereas in patients with wild-type KRAS cancers, left-sided tumors were at decreased risk of death (hazard ratio: 0.81, 95% confidence interval: 0.67-0.97). CONCLUSION: In patients with stage I-III colon cancer, laterality, KRAS mutation, and microsatellite instability status were not independently prognostic after curative resection. However, the effect of laterality was opposite based on KRAS status, with left-sided (compared to right-sided) tumors associated with worse overall survival in mutated KRAS patients and better overall survival in wild-type KRAS individuals. Laterality itself may not be an independent prognostic factor but a reflection of differing genetic profiles within the colon.
BACKGROUND: KRAS mutations, microsatellite instability, and tumor location have been found to be significant prognostic factors in colorectal cancer. The interaction between these variables and its effect on overall survival in nonmetastatic colon cancer has not been well elucidated. METHODS: The National Cancer Database (2010-2016) was queried for patients with stage I-III colon cancer and known microsatellite instability and KRAS status undergoing curative resection. RESULTS: A total of 5,292 patients were identified: 60.4% had right-sided cancers, 36.4% had KRAS mutations, and 15.6% had microsatellite instability. Right-sided tumors were more likely to have microsatellite instability and KRAS mutations compared to left-sided tumors. On univariable analysis, KRAS mutations and microsatellite instability status were not associated with differences in survival, whereas right-sided cancers had worse overall survival compared to left-sided cancers (hazard ratio 1.32, 95% confidence interval: 1.18-1.47). On multivariable analysis, right-sided location, KRAS mutations, and microsatellite instability were not independent prognostic factors. However, a significant interaction between laterality and KRAS status was observed. In patients with mutated KRAS cancers, left-sided tumors were at increased risk of death compared to right-sided tumors (hazard ratio: 1.30, 95% confidence interval: 1.03-1.63), whereas in patients with wild-type KRAS cancers, left-sided tumors were at decreased risk of death (hazard ratio: 0.81, 95% confidence interval: 0.67-0.97). CONCLUSION: In patients with stage I-III colon cancer, laterality, KRAS mutation, and microsatellite instability status were not independently prognostic after curative resection. However, the effect of laterality was opposite based on KRAS status, with left-sided (compared to right-sided) tumors associated with worse overall survival in mutated KRAS patients and better overall survival in wild-type KRAS individuals. Laterality itself may not be an independent prognostic factor but a reflection of differing genetic profiles within the colon.