Microsatellite instability: a predictive marker in metastatic colorectal cancer?

Microsatellite instability (MSI) status is a good prognostic factor for colorectal cancer (CRC), but its predictive value for chemosensitivity remains controversial. We recently performed a meta-analysis (MA) in adjuvant setting showing that MSI high (MSI-H) status did not predict the efficacy of chemotherapy. Studies were identified by electronic search through PubMed, Embase and ASCO proceedings online databases, using several keywords (colorectal cancer, chemotherapy, microsatellite instability). For each study, we calculated the ratio of response rate, complete and partial responses divided by stable disease and progression. Our MA dealt with the predictive value of MSI status on the effect of metastatic chemotherapy using various combinations of 5FU, oxaliplatin or CPT11. From 159 articles and 76 abstracts, we selected only seven independent studies. Data were analysed with a random-effect model (due to heterogeneity between studies) using EasyMA software. Statistical calculations were performed on five studies representing 860 patients (mean age 63 years; 87 MSI-H; 733 microsatellite stable [MSS] tumors). A total of 287 patients received 5FU-based chemotherapy, whereas 574 patients received combinations of 5FU or capecitabine with oxaliplatin and/or irinotecan. Our MA found no benefit of metastatic chemotherapy in terms of response rate for MSI-H patients compared with MSS patients. The global hazard ratio for response rate was 0.83 (95% confidence interval: 0.95; 0.65-1.05; p = 0.11). In conclusion, MSI status did not predict the effect of chemotherapy for metastatic CRC. Metastatic chemotherapy had a similar effect on both MSI-H or on MSS tumors.