PWE-053 Meta-analysis of tumour microsatellite-instability, as a predictor of response to fluorouracil-based adjuvant chemotherapy for colon cancer

Introduction Controversy remain on the use of 5-FU-based regimens in treating microsatellite instability-related colo-rectal cancer, particularly in relation to the effect of patient’s age and of combining 5-FU with other drugs. The aim of this study was to carry out a meta-analysis of current literature to investigate the relationship between tumour microsatellite status and response to 5-FU based adjuvant chemotherapy including patient stratification by staging. Methods A systematic literature review of PubMed was conducted. Studies were included/excluded based on pre-specified criteria. CRC with low MSI (MSI-L) were clustered together with MSS CRC. Overall survival at 5 years was estimated from Keplen-Meier curves. Publication bias was investigated using funnel plots and Egger’s test. Statistical analyses were conducted using the R program (version 3.2.4). Results Out a total of 1807 studies identified in the Pubmed database until December 2018, 326 were reviews or were not written in English and were excluded. Of the 1481 remaining studies, 17 fulfilled the screening criteria. Eight were excluded because they did not include overall survival data at 5 years. Nine studies were therefore used for the meta-analysis. The quality of all studies was considered fair according to pre-defined criteria and Egger’s test revealed no publication bias. There was however considerable variation between studies in terms of study design, tumour site, tumour staging, and molecular techniques used for the identification of MSI. According to the meta-analysis result 5-FU treated individuals who died at 5 years were 0.69 times more likely to have MSI than those who were alive, but this did not reach statistical significance. There were no sufficient studies to carry out subgroup analysis by stage. Conclusions Meta-analysis based on data extracted from published literature is marred by the heterogeneity and/or paucity of clinical, pathological and molecular data in published studies. Similarly to two previous meta-analysis studies there was no significant difference in the overall survival of patients with MSI-H and MSS/MSI-L CRC treated with adjuvant 5-FU. More studies are necessary to clarify whether patients with MSI-H CRC, and in particular those at a relatively early stage, should be offered 5-FU based adjuvant chemotherapy.