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 stageindependent 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 Ps<.0001). After number of pLNs, 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.