Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer

Abstract

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI 85.7–90.4), 93.4% (95%-CI 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi-vs-Lo) = 0.27 (95%-CI 0.18–0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi-vs-Lo) = 0.29, (95%-CI, 0.17–0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi-vs-Lo) = 0.07 (95%-CI 0.01–0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.

Principles of risk assessment in colon cancer: immunity is key

“…We have recently demonstrated the robustness of the consensus Immunoscore (IS) assay in accurately stratifying stage II CC patients into IS-high and -low risk subgroups. 32 , 33 Patients within these subgroups have shown significantly divergent clinical outcomes. 32 , 33 IS is an immune digital pathology (DP)-based assay that quantifies CD3+ and CD8+ lymphocyte infiltration density in both the tumor core and invasive margin.…”

“… 32 , 33 Patients within these subgroups have shown significantly divergent clinical outcomes. 32 , 33 IS is an immune digital pathology (DP)-based assay that quantifies CD3+ and CD8+ lymphocyte infiltration density in both the tumor core and invasive margin. Across all CC stages (I-III), IS assessment has shown a prognostic value significantly superior to all existing prognostic tumor parameters, including the classical AJCC/UICC TNM staging system 34 ( Figure 1(b) ).…”

“…In line with earlier research, 34–37 our recent studies have consistently identified a correlation between a high IS and improved clinical outcomes in all stage II patients. 32 , 33 Particularly, among stage II patients with microsatellite stability (MSS), a high IS was associated with improved DFS and reduced risk of recurrence. Notably, in high-risk stage II patients, IS accurately predicted recurrence risk with High IS exhibiting a remarkably similar recurrence risk to that of low-risk stage II patients.…”

“…This risk was significantly lower than that observed in high-risk stage II patients with Low IS. 32 The high-risk stage II patients classified solely on histopathological features have shown different clinical outcomes. Consequently, the performance of IS contributes to improved patient stratification, 32 potentially guiding clinicians toward optimal treatment options for individual patients.…”

“… 32 The high-risk stage II patients classified solely on histopathological features have shown different clinical outcomes. Consequently, the performance of IS contributes to improved patient stratification, 32 potentially guiding clinicians toward optimal treatment options for individual patients. Moreover, alongside IS, analysis of other immune cell subpopulations such as CD4 Th1 macrophages provides important additional information pertaining to patient survival and response to therapy.…”