Prognostic impact of microsatellite instability in colorectal cancer patients treated with adjuvant FOLFOX.

Abstract

e14005 Background: Microsatellite instability (MSI) results from defective mismatch repair and is observed in 15–20% of colorectal cancers (CRCs). Patients with MSI do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. The standard treatment in adjuvant setting for stage III and for high-risk stage II is FOLFOX according to MOSAIC study. This study aimed to determine the benefit of FOLFOX treatment for MSI compared with Microsatellite stable (MSS) patients in adjuvant setting. Methods: We prospectively analyzed 105 patients who had been treated by adjuvant FOLFOX 4 chemotherapy after curative resection (R0) of CRC between May 2004 and December 2008. MSI phenotype was assessed by measuring the length of five quasi-monomorphic mononuleotidic microsatellite markers (NR21, NR24, NR27, BAT25, BAT26) on an 3100 genetic analyzer (Applied Biosystems). MSI was defined as a reduction in size of three markers or more. Disease Free Survival (DFS) was compared among MSI and MSS patients (Kaplan-Meier). The numbers of 5-year relapses were compared using a chi-square test. Results: Among the 105 tumor specimens, there were 28 (27 %) patients stage II (with high risk of relapse) and 66 (63 %) with stage III. Median age was 66 years. There were 58 men, and 84 colon and 21 rectum cancers; 12 stage II MSI and 8 stage III MSI. MSI patients had significantly less relapses than MSS patients : 2/20 (10 %) compared with 29/82 (36 %) (chi-square = 4.89; p = 0.02). Survival curves for MSI and MSS patients were not statistically different (log-rank = 2.74; p = 0.10). Univariate analysis showed that stage (p = 0.0006) and MSI status (p = 0.01) were statistically significant predictors of DFS, whereas age was not. Multivariate analysis showed that only stage predicted DFS (p = 0.01), with a nonsignificant trend for MSI status (p = 0.08). Conclusions: In this cohort of CRC patients treated with FOLFOX 4, MSI status was associated with a better prognosis in univariate analysis, with a non significant trend in multivariate analysis. Contrasting with previous results obtained with 5-FU alone, the FOLFOX combination used had no detrimental effect. No significant financial relationships to disclose.