Trends and Survival Outcomes of Adjuvant Chemotherapy in Low-Risk Stage II Colon Cancer: A National Cancer Database Analysis

BACKGROUND: Guidelines recommend adjuvant chemotherapy for Stage II colon cancer with high-risk features. However, real-world adherence to these recommendations remains inconsistent. It is unclear whether select low-risk patients still derive survival benefit from adjuvant chemotherapy. OBJECTIVE: Evaluate trends, predictors of use, and survival outcomes associated with adjuvant chemotherapy in patients with low-risk Stage II colon cancer. DESIGN: Retrospective cohort study. SETTINGS: Commission on Cancer-accredited hospitals participating in the National Cancer Database. PATIENTS: Pathological Stage II colon adenocarcinoma patients undergoing definitive resection (2010 to 22) without National Cancer Database-defined high-risk features. INTERVENTIONS: Adjuvant chemotherapy. MAIN OUTCOME MEASURES: Overall survival. RESULTS: There were 7,204/90,724 (7.9%) eligible patients who received adjuvant chemotherapy. Adjuvant chemotherapy use decreased by approximately 30% over the study period, mainly driven by decreased multiagent regimens; single-agent use remained stable. Younger age (< 50) was a significant independent predictor of adjuvant chemotherapy treatment (OR 2.25; p < 0.001), along with KRAS mutation (OR 1.39; p = 0.005) and treatment at nonacademic centers. Conversely, microsatellite instability-high tumors (OR 0.59; p = 0.001) and minimally invasive approaches were each associated with lower odds of receiving adjuvant chemotherapy. Although adjuvant chemotherapy was associated with higher 5-year overall survival in the unadjusted analysis, this association was not significant after adjustment for available covariates (HR 0.998; 95% CI: 0.709-1.404). LIMITATIONS: Retrospective design, lack of disease-specific survival data, limited chemotherapy-related details in the database. CONCLUSIONS: Although adjuvant chemotherapy use in low-risk Stage II colon cancer has decreased over time, it continues to be administered, especially among younger patients. In this retrospective analysis of low-risk Stage II colon cancer, we were unable to identify a survival advantage with chemotherapy. Guideline-defined high-risk criteria, rather than subjective clinical judgement, should remain the basis for treatment decisions. This conclusion is timely given that colorectal cancer has become the most common cause of cancer deaths in patients < 50 years. See Video Abstract.