Contribution of Immunoscore and Molecular Features to Survival Prediction in Stage III Colon Cancer.

BACKGROUND: The American Joint Committee on Cancer staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer.

METHODS: Patient (n = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, sex, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness, KRAS/BRAF , mismatch repair, and Immunoscore (CD3+ , CD8+ T-cell densities). After determining optimal functional form (continuous or categorical) and within Cox models, backward selection was performed to analyze all variables as candidate predictors. All statistical tests were two-sided.

RESULTS: Poorer DFS was found for tumors that were T4 vs T3 (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.19 to 2.60; P  = .004), right- vs left-sided (HR = 1.52, 95% CI = 1.14 to 2.04; P  = .005), BRAF V600E (HR = 1.74, 95% CI = 1.26 to 2.40; P  < .001), mutant KRAS (HR = 1.66, 95% CI = 1.08 to 2.55; P  = .02), and low vs high Immunoscore (HR = 1.69, 95% CI = 1.22 to 2.33; P = .001) (all P  <   .02). Increasing numbers of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both P s<   .0001). After number of +LNs, T stage, and BRAF/KRAS , Immunoscore was the most informative predictor of DFS shown multivariately. Among T1-3 N1 tumors, Immunoscore was the only variable associated with DFS that achieved statistical significance. A nomogram was generated to determine the likelihood of being recurrence-free at 3 years.

CONCLUSIONS: The Immunoscore can enhance the accuracy of survival prediction among patients with stage III colon cancer.