Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study
Menée en France à partir d'échantillons tumoraux prélevés sur 1 322 patients atteints d'un cancer colorectal de stade III traité par chimiothérapie à base d'oxaliplatine, cette étude évalue la performance d'un système de score, basé sur la concentration des lymphocytes CD3+ et CD8+ dans la tumeur et au niveau des marges invasives, pour prédire la survie sans maladie à 3 ans
Background : The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the IDEA France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients.
Patients and Methods : Densities of CD3+ and CD8+ T-cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell’s C-statistics were used to investigate the IS performance.
Results : Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared to Int+High (HR = 1.54; 95% CI 1.24-1.93, P = 0.0001). The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int+High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for gender, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in term of DFS (P = 0.057). IS Int+High significantly predicted benefit of 6 months treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinical low and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus 3-month.
Conclusions : The IS prognostic value for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of FOLFOX6m adjuvant treatment was found in IS Int+High. These results will be validated in an external independent cohort.
Annals of Oncology , article en libre accès, 2020