Current treatment and surveillance modalities are not sufficient for advanced stage III colon cancer: Result from a multicenter cohort analysis.

OBJECTIVE We conducted this multicenter cohort study to evaluate the current tumor-node-metastasis staging system and treatment modality by analyzing the survival outcomes of patient groups with stage III and IV colon cancer. PATIENTS AND METHODS Stage III and IV colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database (SEER cohort) and prospectively maintained Sun Yat-sen University (SYSU) cohort were included in this study. Kaplan-Meier method was used to estimate the cumulative rate of overall survival (OS) between patient groups, and the inverse probability weighting method was used to calculated age and sex-adjusted survival curves. The Cox regression model was used to identify the risk factors for OS. RESULTS A total of 17,911 and 1135 stage III-IV cases were included in the SEER and SYSU cohorts, respectively. Among them, 1448 and 124 resectable stage IV cases underwent curative-intent treatment in the SEER and SYSU cohorts, respectively. The T4N2b group showed a significantly worse survival outcome compared with the M1a subset receiving curative-intent treatment (HR, 1.46; p < 0.001). This finding was validated in the SYSU cohort, in which the T4N2 group had a worse outcome than that of the M1 group receiving curative-intent treatment (HR, 2.44; p < 0.001). These findings were confirmed in the adjusted survival analysis. In the multivariate analysis, the right-side tumor, poor-undifferentiated tumor, and age over 60 years were identified as independent risk factors for T4N2b patients. Based on this multivariate model, the high-risk T4N2b subgroup had a worse survival outcome compared with resectable M1b patients (HR, 1.24; p = 0.03). CONCLUSION By comparing stage III with stage IV colon cancer patients, we identified a subgroup of stage III patients at a higher risk of death than more advanced stages, implying that current cancer care modalities are not sufficient for these high-risk substages.