A prospective blinded study of microsatellite instability (MSI) as a marker of overall survival (OS) in the adjuvant treatment of colorectal cancer (CRC) patients

Abstract

9544 Background: A number of studies have investigated the relationship between MSI and CRC OS. However, results have been inconsistent. This may have been influenced by design issues; specifically, underpowered datasets, retrospective analyses, potential patient selection, and non-blinded investigators. We investigated MSI as a marker of OS in the context of a multi-center randomized phase III trial of 10,000 CRC patients randomized to receive adjuvant portal fluorouracil infusion. Results were pooled with published work from adjuvant clinical trials. Methods: A random subset of 1,000 tissue blocks were centrally collected and anonymized. Tissue was microdissected and MSI status determined by genotyping BAT26 prospective to patient follow-up. Laboratory analyses were performed blinded to all clinical data. OS data was pooled with that from studies investigating MSI status in adjuvant clinical trials by standard meta-analysis techniques. Results: Efficacy data from the clinical trial has yet to report. 543 samples have been genotyped to date. 15% of tumors are MSI+. Median follow-up was 55 months. CRCs with MSI tended to have a better OS (HR=0.77, 95% CI:0.48–1.24). This was more pronounced for colonic tumors (HR=0.60, 95% CI:0.30–1.19; rectal tumors HR=1.12, 95% CI:0.58–2.13). Pooling our results with OS data from 3 adjuvant trials (n=1,684, MSI= 326) confirmed a significant survival advantage for MSI+ tumors (HR=0.76, 95% CI:0.61–0.94, phet=0.84, I2=0%). Conclusions: MSI is a marker for improved OS in stage II/III CRC. Additional prospective studies are required to define the role of adjuvant chemotherapy in these tumors. No significant financial relationships to disclose.