Is There a Role for Neoadjuvant Systemic Therapy for cT4bM0 Colon Cancer? A Propensity Score-Matched Analysis of the National Cancer Database.

Abstract

Non-metastatic T4b colon-cancer has been traditionally treated with upfront surgery, often requiring technically challenging multiorgan resection. Neoadjuvant chemotherapy can potentially downsize and improve resectability of those tumors.To explore trends and outcomes of neoadjuvant chemotherapy use in non-metastatic T4b colon cancer patients, compared to upfront surgery. To determine factors associated with increased neoadjuvant chemotherapy use and with overall survival.Retrospective cohort-study.Conducted using the National Cancer Database.Non-metastatic T4b colon cancer patients who underwent colectomy (2006-2016). Patients receiving neoadjuvant chemotherapy were propensity-matched (1:2) to those who underwent upfront surgery, in either clinical node-negative or node-positive disease.Postoperative outcomes (length of stay, 30-day readmission, 30/90-day mortality), oncologic resection adequacy (R0-rate, number of resected/positive nodes), and overall-survival.Neoadjuvant chemotherapy was used in 7.7% of the patients. Neoadjuvant chemotherapy use increased over the study period from 4% to 16% in the entire cohort; from 3% to 21% in patients with clinical node-positive disease; and from 6% to 12% in patients with clinical node-negative disease. Factors associated with increased use of neoadjuvant chemotherapy included younger age (OR0.97,95%CI:0.96-0.98, p < 0.001), male gender (OR1.35,95%CI:1.11-1.64, p = 0.002), recent diagnosis year (OR1.16,95%CI:1.12-1.20, p < 0.001), academic centers (OR2.65,95%CI:2.19-3.22, p < 0.001), clinical node-positive (OR1.23,95%CI:1.01-1.49, p = 0.037), and tumor located in sigmoid colon (OR2.44,95%CI:1.97-3.02, p < 0.001). Patients who received neoadjuvant chemotherapy had significantly higher R0 resection compared with upfront surgery (87%vs.77%, p < 0.001). On multivariable analysis, neoadjuvant chemotherapy was associated with higher overall-survival (HR0.76,95%CI:0.64-0.91, p = 0.002). On propensity-matched analyses, neoadjuvant chemotherapy was associated with a higher 5-year overall-survival compared to upfront surgery in patients with clinical node-positive disease (57% vs.43%, p = 0.003) but not in clinical node-negative disease (61% vs.56%, p = 0.090).Retrospective design.Neoadjuvant chemotherapy use for non-metastatic T4b has increased significantly on the national level, more so in patients with clinical node-positive disease. Patients with node-positive disease treated with neoadjuvant chemotherapy had higher overall-survival compared to upfront surgery.