Prognostic Value of a Seven-Factor Risk Stratification System in T3N0 Colon Cancer: A Single-Center Retrospective...

Background and Objectives: This study aimed to validate the prognostic value of clinicopathologic risk factors and assess the discriminatory performance of a guideline-based seven-factor risk stratification system in T3N0 colon cancer. Secondary objectives included examining the independent prognostic role of mucinous histology and analyzing current adjuvant chemotherapy decision-making patterns. Materials and Methods: A total of 174 patients who underwent curative resection between 2015 and 2025 and were diagnosed with pathologic T3N0M0 (stage IIA) colon adenocarcinoma were retrospectively reviewed. Patients with T4 disease, rectal tumors, synchronous malignancies, neoadjuvant therapy and mismatch repair deficiency (dMMR/MSI-H) were excluded. Seven high-risk factors were defined: lymphovascular invasion (LVI), perineural invasion (PNI), intestinal obstruction, perforation, inadequate lymph node sampling (<12 lymph nodes), poor differentiation (Grade 3 and 4), and high-grade tumor budding (BD3, ≥10 buds according to ITBCC criteria). Mucinous histology was evaluated as a separate subgroup analysis. The primary endpoint was recurrence-free survival (RFS); secondary endpoints were disease-free survival (DFS) and overall survival (OS). Competing risks analysis was performed using the Aalen-Johansen estimator, with death without recurrence as the competing event. Results: The median follow-up was 43.7 months. Five-year RFS rates were 97.1%, 92.8%, and 70.0% in the low-, intermediate-, and high-risk groups, respectively (log-rank p = 0.041). Five-year OS rates were 87.2%, 88.6%, and 69.9%, respectively (log-rank p = 0.0004). Five-year cumulative incidence of recurrence in competing risks analysis was 2.9%, 7.1%, and 26.0%, respectively. Five-year DFS rates were 87.2%, 83.1%, and 54.2% (log-rank p = 0.0003). In multivariate DFS analysis, intestinal obstruction (HR = 4.26; 95% CI: 2.05-8.87; p < 0.001) and tumor budding (HR = 3.77; 95% CI: 1.67-8.53; p = 0.001) were independent prognostic factors; consistent but exploratory RFS estimates were observed (obstruction HR = 8.51; 95% CI: 2.50-28.96; p = 0.001; tumor budding HR = 5.48; 95% CI: 1.72-17.44; p = 0.004), derived from 12 recurrence events and therefore prone to overfitting. As a continuous variable, each 1-unit increase in the seven-factor risk score increased the RFS hazard 1.74-fold (95% CI: 1.21-2.51; p = 0.003; RFS C-index = 0.656; 95% CI: 0.489-0.830). A parsimonious two-factor model (obstruction + tumor budding) achieved a higher C-index of 0.760 (95% CI: 0.569-0.921) for RFS. Mucinous histology was present in 17 patients (9.8%) and showed no recurrence events. Adjuvant CT rates increased significantly with higher risk scores (p = 0.002). Conclusions: Guideline-based seven-factor risk stratification demonstrates statistically significant, though modest, discriminatory performance (RFS C-index = 0.656; 95% CI: 0.489-0.830; DFS C-index = 0.646; 95% CI: 0.519-0.778) in pMMR T3N0 colon cancer. Intestinal obstruction and tumor budding are independent prognostic factors that effectively stratify patients by recurrence risk; a parsimonious two-factor model based on these two features matched or exceeded the discrimination of the full score. The seven-factor system should be regarded as a validation of guideline-defined high-risk features that may support adjuvant chemotherapy discussions in stage IIA colon cancer; external validation is required before clinical implementation.