Tumor Deposits in Stage III Colon Cancer: Correlation With Other Histopathologic Variables, Prognostic Value, and Risk Stratification—Time to Consider “N2c”

OBJECTIVES: National Comprehensive Cancer Network (NCCN) guidelines for stage III colon cancer define low-risk versus high-risk patients based on T (1 to 3 vs. 4) and N (1 vs. 2) status, with some variations in treatment. This study analyzes the impact of tumor deposits (TDs), T and N status, poor differentiation (PD), perineural invasion (PNI), and lymphovascular invasion (LVI) on survival. MATERIALS AND METHODS: A retrospective analysis (2010-2015) of the National Cancer Database of stage III colon cancer patients treated with both surgery and chemotherapy was conducted. Data was extracted on sex, race, age at diagnosis, Charlson-Deyo Score, histopathologic variables, and survival rates. Statistical analysis used the test of proportions, log-rank test for Kaplan-Meier curves, and Cox proportional hazard models. RESULTS: For the 42,901 patients analyzed, 5-year survival rates were similar for LN(+)TD(−) (59.8%) and LN(−)TD(+) (58.2%), but significantly worse for LN(+)TD(+) (41.5%) (P<0.001). The presence of LN(+)TD(+) was more often associated with T4 (36.9%), N2 (55.1%), PD(+) (37.4%), PNI(+) (34.5%), and LVI(+) (69.1%), than LN(+)TD(−) or LN(−)TD(+) (P<0.001). The hazard ratios for each variable were: TD: 1.34; T4: 1.71; N2: 1.44; PD(+): 1.37; PNI: 1.11; LVI(+): 1.18. LN(−) patients with ≥3 TD(+) (N1c) had worse overall survival than those with 1 to 2 TD(+) (P<0.01), but similar to ≥4 LN(+)TD(−) (N2) and 1 to 3 LN(+)TD(+) (N1a-b). In our model, 5-year survival ranged from 23.4% for high-risk to 78.1% for low-risk patients (P<0.001). CONCLUSION: This National Cancer Database (NCDB) analysis offers greater risk stratification and may prompt consideration of changes in American Joint Committee on Cancer (AJCC) classification (N2c, in addition to N1c) to reflect the different prognosis and guide management, as well as survivorship strategies, for TD(+) stage III colon cancer patients.