Stage III colon cancer, defined under the TNM classification by the involvement of regional lymph nodes, carries a risk of recurrence that varies from one patient to another. Conventional histopathological parameters are not always sufficient to predict outcome or to guide the decision regarding adjuvant chemotherapy. The density of tumor-infiltrating lymphocytes is a recognized prognostic factor: the Immunoscore, a standardized measure based on the quantification of CD3+ T cells and CD8+ cytotoxic T cells in the tumor core and at its invasive margin, is specifically intended to incorporate this immune information into patient assessment.
This international study, conducted under the auspices of the Society for Immunotherapy of Cancer, evaluated the consensus Immunoscore in 763 patients with stage III colon cancer, divided into two cohorts (Canada/United States and Europe/Asia). Lymphocyte densities were quantified by digital pathology. The primary endpoint was time to recurrence; secondary endpoints included overall survival, disease-free survival, prognosis in patients with microsatellite-stable status, and the predictive value for chemotherapy efficacy.
Patients with a high Immunoscore had the lowest risk of recurrence in both cohorts. Three-year recurrence-free survival rates reached 56.9%, 65.9%, and 76.4% for low, intermediate, and high Immunoscores, respectively (hazard ratio high versus low: 0.48; P = .0003). A high Immunoscore was significantly associated with a longer time to recurrence, overall survival, and disease-free survival (all P < .001). In a multivariate Cox analysis stratified by center, this association remained independent of sex, T stage, N stage, sidedness, and microsatellite instability status (HR: 0.41; P = .0003). It remained significant among patients with microsatellite-stable status alone (HR: 0.36; P = .0003). Among all variables, the Immunoscore made the strongest contribution to the influence on survival. Chemotherapy was significantly associated with survival in the high-Immunoscore group, both in low-risk patients (HR chemotherapy versus none: 0.42; P = .0011) and in high-risk patients (HR: 0.5; P = .0015), in contrast to the low-Immunoscore group (P > .12).
This work establishes that a high Immunoscore is significantly associated with prolonged survival in stage III colon cancer. It further suggests that patients with a high Immunoscore are those who derive the greatest benefit from chemotherapy in terms of reducing the risk of recurrence.