Do Tumor Deposits Demand More? Association of Chemotherapy Regimen Intensity with Survival Outcomes in N1 Colon...

Tumor deposits (TDs) in stage III colon cancer are associated with worse outcomes, yet the American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) system only accounts for TDs as N1c in the absence of positive lymph nodes. The Sassun-Mayo staging system integrates TDs with nodal count, often upstaging N1 patients to N2; however, therapeutic implications remain unclear as chemotherapy regimens differ between stages.

This retrospective, multicenter, cohort study included patients with AJCC stage III N1 colon adenocarcinoma with one or more TD. Exclusion criteria were age >75 years, inadequate chemotherapy, and no follow-up. Patients were categorized as 'treated as N1' (3 months of FOLFOX or 6 months of capecitabine/5-fluorouracil) versus 'treated as N2' (6 months of FOLFOX or 3-6 months of XELOX).

In total, 110 patients were included; 27 (25%) were treated as N1, and 83 (75%) were treated as N2, with balanced baseline characteristics. Patients receiving N2-level chemotherapy had better 5-year outcomes than receiving N1 chemotherapy protocols. Overall survival was 87.5% versus 67.6% (p = 0.010), and disease-free survival was 81.3% versus 61.2% (p = 0.023). In multivariable analyses adjusted for pT stage, N2-level therapy was associated with a lower risk of death (hazard ratio [HR] 0.31; 95% confidence interval [CI] 0.12-0.79; p = 0.015) and recurrence (HR 0.41; 95% CI 0.19-0.92; p = 0.031). We found that 3-6 months of XELOX yielded the highest disease-free survival, whereas capecitabine/5-fluorouracil and 3 months of FOLFOX were associated with the poorest outcomes.

Patients with TD-positive N1 colon cancer may benefit from N2-level chemotherapy. Incorporating TDs into nodal count may refine prognostic accuracy and improve treatment selection, potentially warranting updates to staging guidelines.