Stage III colon cancer is treated after surgery with adjuvant chemotherapy combining a fluoropyrimidine and oxaliplatin. The recommended duration of this treatment currently relies on a classification into two risk groups defined by T and N stages: clinically low-risk tumors (T1-3 N1), for which three months of treatment are advised, and high-risk tumors (T4 and/or N2), which warrant six months of chemotherapy. This stratification nevertheless remains imperfect for estimating individual patient prognosis. The Immunoscore, which quantifies by digital image analysis the densities of CD3+ and CD8+ T lymphocytes at the tumor center and at its invasive margin, has already been validated as an independent prognostic variable in stage I to III colorectal cancer and has been incorporated into the ESMO clinical practice guidelines for localized colon cancer. The authors sought to determine whether this tool could refine prognosis within the clinical risk groups themselves.
To this end, 600 patients with resected stage III colon carcinoma were randomly selected from the FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) chemotherapy arm of the phase III NCCTG N0147 trial. Recurrence-free survival was analyzed according to the Immunoscore using a multivariate Cox regression model, applied separately to each risk group, with adjustment for several covariates including KRAS, BRAFV600E, and DNA mismatch repair status.
Among the 559 tumors with available Immunoscore data, 53.5% were clinically low-risk and 46.5% were high-risk. In both groups, a low Immunoscore was associated with significantly poorer five-year recurrence-free survival than a high Immunoscore: 77.5% versus 91.8% in low-risk patients (hazard ratio 1.70; 95% CI: 1.03-2.79; p = 0.037), and 55.3% versus 70.3% in high-risk patients (hazard ratio 1.65; 95% CI: 1.11-2.47; p = 0.013). Notably, low-risk tumors with a low Immunoscore showed an outcome comparable to that of high-risk tumors with a high Immunoscore. Adding the Immunoscore to clinical risk parameters and a limited number of biomarkers significantly improved the prognostic capacity of the multivariate models (likelihood ratio test, p = 0.0003).
These results indicate that the Immunoscore refines patient prognosis beyond clinical risk group classification alone, suggesting its potential usefulness for guiding therapeutic decisions in the adjuvant setting.