Shifting Paradigm: Utilization and Outcomes with Neoadjuvant Chemotherapy for cT4 and cN2 Colon Cancers

Upfront surgical resection (USR) remains the standard of care for resectable, nonmetastatic colon cancer. However, for locally advanced (cT4) and high nodal burden (cN2) disease, we hypothesized that neoadjuvant chemotherapy (NAC) would be associated with better overall survival compared with USR followed by adjuvant chemotherapy (AC).

We queried the National Cancer Database for nonmetastatic, microsatellite stable cT4 or cN2 colon cancer treated with USR followed by AC or NAC followed by surgical resection. Univariate and multivariate logistic regression was utilized to determine covariates associated with receipt of NAC and with death. Propensity score matching (PSM) was used for overall survival (OS) analysis.

A total of 10,394 patients with cT4 disease (8299 USR and 2095 NAC) and 7574 patients with cN2 disease (6205 USR and 1369 NAC) met criteria for study inclusion. Patients who were younger, healthier, and treated at academic centers were more likely to receive NAC. For both cohorts, NAC was associated with reduced margin positivity (cT4: 12.5% versus 20.5%, p < 0.001; cN2: 7.8% versus 12.5%, p < 0.001) and reduced positive lymph node ratio (LNR) (cT4: 8.7% versus 18.7%, p < 0.001; cN2: 17.3% versus 39%, p < 0.001). NAC was associated with better OS for cT4 (p = 0.003) and cN2 disease (p < 0.001), particularly cT3N2 and cT4N2.

Among cT4 and cN2 colon cancers, NAC was associated with reduced margin positivity, decreased lymph node ratio, and better OS. Our findings support the need for further investigation of NAC for locally advanced and high nodal burden colon cancers.