Conditional Overall Survival After Diagnosis of Non-Metastatic Colon Cancer: Impact of Laterality, MSI, and KRAS Status

Background: The prognostic relevance of laterality, microsatellite instability (MSI), and KRAS status in colon cancer has been established. However, their effect on conditional overall survival (COS) remains unknown. Methods: COS is the probability of surviving additional years after a time from diagnosis. The National Cancer Database (2010–2017) was queried for adults with non-metastatic colon cancer and known mutation status undergoing curative resection. COS was investigated at 2 years. Results: Of 4838 patients, 3716 survived at least 2 years: 15% had stage I, 38% stage II, and 46% stage III disease. Fifty-nine percent had a right-sided tumor, 16% were MSI-high, and 37% were mutated KRAS (mKRAS). The proportion of patients alive at 2 years was higher for stage I compared with stage II and III (65 vs. 61 vs. 54%). The 5-year overall survival for stage I–III was 80, 76, and 67% for the initial cohort, and 90, 88, and 86% for those alive at 2 years. After adjustment, higher pathologic T and N stage, tumor deposits, and no chemotherapy were associated with worse COS (p < 0.01). While laterality and MSI status were not associated with COS, mKRAS was independently associated with decreased COS (HR 1.35, 95% CI 1.12–1.62). Conclusion: Patients with mKRAS had worse COS, suggesting that these mutations confer an aggressive biologic behavior, with patients remaining at higher risk of death 2 years after diagnosis. Routine evaluation of KRAS status should be considered in patients with non-metastatic disease for prognostication and to identify those who might benefit from modified surveillance protocols.