Considerations in Neoadjuvant Therapy Implementation in T3 and T4 Colon Cancer

PURPOSE Neoadjuvant chemotherapy (NAC) is increasingly being considered over standard upfront surgery followed by adjuvant chemotherapy for locally advanced colon cancer. Studies have been underpowered to look at the effect of NAC on overall survival (OS) in individual clinical T stages. METHODS A nationwide retrospective analysis using the National Cancer Database from 2010 to 2020 to evaluate patients with clinical stage T3-4, N0-2, M0 colon adenocarcinomas in line with the FOxTROT trial. Cox proportional hazards model was used to evaluate the effect of NAC approach compared with upfront surgery on OS. Clinical and pathological T stages were compared among those who underwent upfront surgery to evaluate the accuracy of clinical T staging. RESULTS A total of 60,557 patients were identified—2,313 patients undergoing NAC and 58,245 undergoing upfront surgery. In the past decade, use of NAC increased from 1.73% to 12.13%. In our multivariable survival analysis combining clinical T3 and T4 patients, we observed a worse OS in the NAC group (hazard ratio [HR], 1.16 [95% CI, 1.07 to 1.26]). We found no OS benefit for patients undergoing NAC approach for clinical stage T3 (HR, 1.13 [95% CI, 0.99 to 1.28]) but found a significant OS benefit for patients undergoing NAC approach for clinical stage T4 (HR, 0.85 [95% CI, 0.77 to 0.95]). DISCUSSION Our analysis demonstrated OS benefit of the NAC approach in T4 colon adenocarcinoma but not in T3. This study highlights the importance of evaluating the survival benefit of NAC separately for T3 and T4 colon adenocarcinoma in future studies.