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

• Published in: Annals of surgical oncology Vol. 31; no. 1; pp. 142 - 151
• Main Authors: Tran, Catherine G., Goffredo, Paolo, Mott, Sarah L., Suraju, Mohammed O., Kohn, Julia F., Mishra, Aditi, Vauthey, Jean-Nicolas, Hassan, Imran
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2024; Springer Nature B.V
• Subjects: Adult; Aggressive behavior; Chemotherapy; Colon cancer; Colonic Neoplasms - pathology; Colorectal cancer; Diagnosis; Genes, ras; Hepatobiliary Tumors; Humans; K-Ras protein; Medicine; Medicine & Public Health; Metastases; Metastasis; Microsatellite Instability; Mutation; Neoplasm Staging; Oncology; Prognosis; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Surgery; Surgical Oncology; Survival; Tumors
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-023-14443-x

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 (m KRAS ). 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, m KRAS was independently associated with decreased COS (HR 1.35, 95% CI 1.12–1.62). Conclusion Patients with m KRAS 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.