Currently, the risk of recurrence after surgery for patients with colorectal cancer (CRC) is estimated based on histopathological criteria of tumor invasion according to the American Joint Committee on Cancer (AJCC) and TNM classification system and on features of tumor cell differentiation. In recent years, the role of the immune system in cancer patient outcomes has been appreciated, and in CRC the strength of adaptive immune reaction in the colon and in the invasive margin is strongly correlated with time to recurrence and overall survival (OS). The consensus Immunoscore, a scoring system that quantifies the density of effector T-cells within the tumor, has been developed as a potential prognostic model to predict risk of recurrence in patients with TNM stage I-III CRC.
In an international validation study to assess the accuracy of the Immunoscore system, tissue samples from 2681 patients with stage I-III CRC were evaluated by Immunoscore, and results correlated with patient outcomes. Half of the patients (51%) had an intermediate Immunoscore, while 22% had a low Immunoscore and 27% had a high Immunoscore. In the training set (n = 700), high Immunoscore was associated with a significantly reduced 5-year rate of recurrence, compared to low Immunoscore (8% vs 32%; HR 0.20, P<.0001). Patients with an intermediate Immunoscore had a 19% risk of recurrence at 5 years (HR vs high: 0.38, P = .0011). Five-year OS rate was also significantly improved in patients with a high Immunoscore, compared to those with low (82% vs 62%; HR 0.53, P = .0004) and intermediate (82% vs 77%; P = .035) Immunoscores.
Results from the training set were consistent in both the internal (n = 636) and external (n = 1345) validation sets. The Immunoscore assay was highly reproducible between different observers and centers (r = .97 for both tumor and invasive margin). Multivariate analysis found that the association of high Immunoscore with increased time to recurrence was independent of patient age, sex, T or N stage, microsatellite instability, or existing prognostic factors. Immunoscore was more closely associated with risk of recurrence than any other clinical parameter, including TNM classification.
The investigators concluded that Immunoscore is a better and more reliable method of estimating the risk of recurrence in patients with CRC, and that these data support adoption of a new “TNM-Immune” method of CRC classification. In an accompanying commentary, the authors agreed that findings from this study support Immunoscore as a prognostic biomarker in colon cancer that can be standardized across pathology laboratories. The role of Immunoscore as a potential predictive biomarker for response to therapy has yet to be identified. Lancet. 2018 May 10 [Epub ahead of print].