Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer

Abstract

PURPOSE The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR). METHODS An international study led by the Society for Immunotherapy of Cancer evaluated the predefined consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy. RESULTS Patients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high v low], 0.48; 95% CI, 0.32 to 0.71; P = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all P < .001). In Cox multivariable analysis stratified by participating center, Immunoscore association with TTR was independent (HR [high v low], 0.41; 95% CI, 0.25 to 0.67; P = .0003) of patient’s sex, T stage, N stage, sidedness, and microsatellite instability status. Significant association of a high Immunoscore with prolonged TTR was also found among MSS patients (HR [high v low], 0.36; 95% CI, 0.21 to 0.62; P = .0003). Immunoscore had the strongest contribution χ2 proportion for influencing survival (TTR and OS). Chemotherapy was significantly associated with survival in the high-Immunoscore group for both low-risk (HR [chemotherapy v no chemotherapy], 0.42; 95% CI, 0.25 to 0.71; P = .0011) and high-risk (HR [chemotherapy v no chemotherapy], 0.5; 95% CI, 0.33 to 0.77; P = .0015) patients, in contrast to the low-Immunoscore group ( P > .12). CONCLUSION This study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.

ctDNA and Adjuvant Therapy for Colorectal Cancer: Time to Re-Invent Our Treatment Paradigm

“…Stage I to III CRC with high Immunoscore has been shown to be associated with lower recurrence risk than tumours with low Immunoscore (HR, 0.20; p < 0.0001) [ 97 ]. More specifically for patients with stage III disease, a recent retrospective series including patients untreated and those treated with a variety of adjuvant chemotherapy regimens reported 3-year recurrence-free rates of 56.9% and 76.4% in patients with low and high Immunoscores, respectively (HR, 0.48; p < 0.0003) [ 98 ]. A separate analysis in the high-risk stage II (T4N0) subset demonstrated a 5-year recurrence rate of 84.6% in patients with intermediate/high Immunoscore and 46.3% in patients with low Immunoscore [ 99 ].…”

Prognostic and Predictive Cross-Roads of Microsatellite Instability and Immune Response to Colon Cancer

“…Namely, patients showing high GrB + lymphocytes and MSI phenotype were those showing the more favorable relapse-free rates [ 27 ]. Other researches [ 54 ] pointed to the association of high load of TILs (assessed as intraepithelial CD8 + cells) with better long-term outcome of colon cancer patients. Furthermore, in light of the temporal pattern of the reduced risk associated with high CD8 + TILs (that became significant only after 2 years), they hypothesized an immune surveillance towards micro-metastases strongly correlated with the local amount of CD8 + cells.…”

Usefulness and robustness of Immunoscore for personalized management of cancer patients

“…[11][12][13][14] Indeed, the international Immunoscore consortium recently demonstrated that Immunoscore predicted survival and response to chemotherapy in 763 Stage III colon cancer (CC) patients. 15 The prognostic value of Immunoscore was confirmed in two independent phase 3 clinical trials (NCCTG-N0147, n = 559; Prodige-IDEA, n = 1062). 16,17 Moreover, results from IDEA phase 3 randomized trial revealed the predictive value of Immunoscore for response to adjuvant FOLFOX chemotherapy duration.…”