Neoadjuvant therapy in T3 and T4 colon cancer: Is there a promising future?

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Background: 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 impact of NAC on overall survival (OS) in individual clinical T stages. Methods: A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T3 and T4 colon adenocarcinomas from 2010 to 2020. Cox proportional hazards model was used to evaluate the impact of NAC approach compared to upfront surgery on OS. Clinical and pathological T stages were compared among those who underwent upfront surgery to evaluate accuracy of clinical T staging. Results: 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 (HR 1.16, 95% CI 1.07-1.26). We found no OS benefit for patients undergoing NAC approach for clinical stage T3 (HR 1.13, 95% CI 0.99-1.28) but found a significant OS benefit for patients undergoing NAC approach for clinical stage T4 (HR 0.85, 95% CI 0.77-0.95). We observed that clinical T4 stage was accurately staged in 90.48% with overstaging in 9.52%; clinical T3 stage was accurately staged in 95.24% with overstaging in 2.18% of patients. Conclusions: Our analysis demonstrated OS benefit of the NAC approach in T4 colon adenocarcinoma but not in T3. The study highlights the importance of evaluating survival benefit of NAC separately for T3 and T4 colon adenocarcinoma in future studies, and the challenges of accurate clinical staging of colon cancer for NAC planning.