Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data

Background and methodsWe have reviewed and pooled data from published studies to evaluate the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Thirty-one eligible studies reporting survival in 12782 patients characterised for MSI were pooled using a fixed- or random-effects model.ResultsThe summary odds ratio (OR) estimate for overall survival (OS) associated with MSI was 0.6 (95%CI 0.53–0.69, p < 0.0001), with no evidence of heterogeneity. The effect was similar for disease-free survival (DFS) (OR = 0.58, 95%CI 0.47–0.72, p < 0.0001). In a subset of patients treated with 5-fluorouracil (5-FU)-based chemotherapy a significant improved prognosis was found for microsatellite stable (MSS) tumours (OR = 0.52, 95%CI 0.4–0.6, p < 0.0001) with no heterogeneity (p = 0.53; I2 = 0%). By contrast a large heterogeneity characterised the data relative to 396 patients with MSI tumours (OR = 0.69, 95%CI 0.3–1.5, p = 0.1; heterogeneity: p = 0.03; I2 = 58%).ConclusionsThis study confirmed the association between MSI and favourable prognosis as determined by both OS and DFS of CRC patients. A significant beneficial effect of 5-FU therapy was found for MSS tumours whilst no clear conclusion was reached for MSI tumours due to the high inter-study heterogeneity. We propose that this inconclusive result is due to the use of a single marker, such as MSI, that cannot account alone for the complexity of the mechanisms underlying 5-FU cytotoxicity. Future studies to predict response to 5-FU chemotherapy should include additional genome stability markers.