Does microsatellite instability predict the effect of adjuvant chemotherapy in stage III colorectal cancer? A meta-analysis

Abstract

4121 Background: Microsatellite instability (MSI) is a prognostic factor in colorectal cancer. Whether it predicts the effect of adjuvant chemotherapy (CT) on overall survival (OS) and relapse-free survival (RFS) is controversial. Methods: Studies were identified by an electronic search using online PubMed, with simultaneous keywords (colorectal neoplasm, microsatellite instability, chemotherapy, prognosis). Abstracts from ASCO and AACR proceedings were reviewed. Articles were obtained from cross-checking of references and from a previous prognostic meta-analysis (MA) (Popat, 2005). We used EasyMA software, available online. A Hazard Ratio (HR) < 1 for MSI-high (MSI-H) status compared with microsatellite stable (MSS) meant a better survival. Results: Our MA found 21 studies (4 abstracts). Statistical calculations were performed in 11 studies (5087 patients including 2879 receiving 5FU-based CT; mean age: 63 years; 1489 stage II, 2648 stage III (64%)). MSI-H was found in 644 patients (15% of total), MSS in 3624. Seven studies (2 randomized) assessed 2 cohorts receiving or not adjuvant CT, 4 studies only included patients receiving CT. Global HR OS (9 studies) was 0.79 (95% confidence interval or CI: 0.64–0.98; p = 0.03). Global HR RFS (8 studies) was 0.67 (95% CI: 0.54–0.83; p < 0.001). A MA on stage III patients (4 studies, 719 patients, 137 MSI-H) found a higher survival among MSI-H than MSS patients receiving CT (HR OS: 0.71, 95% CI 0.49–1.03; HR RFS 0.56, 95% CI 0.42–0.75). Interaction between MSI status and CT status was statistically significant on OS and RFS (4 studies). A MA among MSI-H patients (7 studies) found no survival difference between patients under CT or not: HR OS: 0.70 (95% CI 0.44–1.09), HR RFS: 0.96 (95% CI: 0.62–1.49). Conclusions: Adjuvant CT significantly improved survival in MSI-H compared with MSS patients. MSI-H stage III patients receiving CT survived more than MSS. MSI-H status did not predict response to CT compared with no treatment. No significant financial relationships to disclose.