KRAS Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803

Introduction

KRAS mutations are common in colorectal cancer, with approximately 30-40% of colon cancers harboring mutations in codons 12 and 13 of KRAS. While KRAS mutation in metastatic colorectal cancer predicts resistance to anti-EGFR targeted therapy, its prognostic role in colon cancer independent of anti-EGFR therapy has been controversial.

Methods

This study analyzed 508 cases from 1264 patients with stage III colon cancer enrolled in the CALGB 89803 trial, which compared adjuvant chemotherapy regimens of 5-fluorouracil and leucovorin with or without irinotecan. KRAS mutations were detected in 178 tumors (35%) using Pyrosequencing. The study assessed the prognostic significance of KRAS mutation, adjusting for potential confounders such as age, sex, tumor location, and microsatellite instability (MSI) status.

Results

Patients with KRAS-mutated tumors did not experience any significant difference in disease-free survival (DFS), recurrence-free survival (RFS), or overall survival (OS) compared to those with KRAS-wild-type tumors. Five-year DFS, RFS, and OS rates were similar between the two groups. The effect of KRAS mutation on survival did not significantly differ based on clinical features, chemotherapy arm, or MSI status.

Discussion

The findings suggest that KRAS mutational status does not have a substantial prognostic or predictive role in stage III colon cancer treated with adjuvant chemotherapy. This is consistent with most previous large studies on colon cancers, indicating that while KRAS mutation is a critical biomarker for predicting response to anti-EGFR therapy in metastatic colorectal cancer, it does not significantly predict patient prognosis in stage III colon cancer.

Conclusion

In conclusion, KRAS mutational status did not significantly predict clinical outcome in this study of stage III colon cancer patients. Although KRAS mutational testing is crucial for assessing the appropriateness of anti-EGFR therapy in advanced colorectal cancer, KRAS status is unlikely to meaningfully predict patient prognosis in stage III colon cancer.