A meta-analysis of microsatellite instability and colorectal cancer prognosis

Abstract

9576 Background: A number of studies have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Although many have reported an improved overall survival with MSI, estimates of the hazard ratio (HR) between studies differ. To derive a more precise estimate of the prognostic significance of MSI, we have reviewed published studies and carried out a meta-analysis of the published literature. Methods: Studies stratifying survival in CRC patients by MSI status were eligible for analysis. The principle outcome measure was the HR. Data from eligible studies were pooled using standard meta-analysis techniques. Results: Thirty-two eligible studies reported survival in a total of 7642 cases, including 1277 with MSI. Studies varied greatly in size (median 159, range 30–1000). There was no evidence of publication bias (p>0.1, Egger's test). MSI was associated with a better prognosis. The combined HR estimate for overall survival associated with MSI was 0.65 (95% CI: 0.59–0.71, heterogeneity p=0.16, I2=20%). This benefit was maintained restricting analyses to clinical trial patients (HR=0.69, 95% CI: 0.56–0.85) and patients with locally advanced CRC (HR=0.67, 95% CI: 0.58–0.78). In patients treated with adjuvant 5-fluorouracil (5FU) CRCs with MSI had a better prognosis (HR=0.72, 95% CI: 0.61–0.84). While data is limited, adjuvant 5FU showed a significant benefit in tumors without MSI (HR=0.72, 95% CI: 0.57–0.92), but no benefit in tumors with MSI (HR=1.24 95% CI: 0.72–2.14). Conclusions: CRCs with MSI have at least a 15% improved survival compared to those with intact mismatch repair. Additional studies are needed to further define the benefit of adjuvant chemotherapy in locally advanced tumors with the MSI phenotype. No significant financial relationships to disclose.