Microsatellite Instability in Stage 3 Colon Cancer

Microsatellite Instability in Patients with Stage III Colon Cancer Receiving Fluoropyrimidine with or without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials

In patients with stage III colon cancer, whose tumors demonstrate microsatellite instability the authors sought to determine the efficacy of adjuvant fluoropyrimidine with or without oxaliplatin as well as the prognostic value of MSI.

Materials and methods:
Individual patient data from the ACCENT clinical trial database was used.  Disease-free survival and overall survival were calculated using stratified cox models adjusted for demographics and clinicopathologic factors.

MSI status was available for 5,457 patients.  Microsatellite instability was seen in 609 patients, 11.2%.  The remainder were microsatellite stable.  12 clinical trials were reviewed.  Oxaliplatin significantly improved overall survival of microsatellite unstable patients from 2 randomized clinical trials, with 185 total patients, adjusted hazard ratio of 0.5 to, 95% confidence interval, 0.28–0.93.  among 4,250 patients treated with fluoropyrimidine plus oxaliplatin, 461 MSI and 3,789 MSS, MSI was associated with better overall survival in the N1 group compared with MSS, adjusted hazard ratio 0.66, but similar survival in the N2 population, adjusted hazard ratio 1.13, P – value of interaction = 0.029.  The main independent prognosticators of MSI patients treated with fluoropyrimidine plus oxaliplatin was T-stage, adjusted hazard ratio 2.09, and N-stage, adjusted hazard ratio 3.57.  Similar results were seen with disease-free survival.

The authors concluded “adding oxaliplatin to fluoropyrimidine improves overall survival and disease-free survival in patients with microsatellite instability stage III colon cancer.  Compared with microsatellite stable patients, microsatellite instability patients experience better outcomes in N1 group but similar survival in the N2 group”