Active Specific Immunotherapy, given as adjuvant treatment, improves survival of patients with microsatellite stable colorectal tumors, but not of patients with microsatellite instable colorectal tumors

Abstract

It has been documented that Active Specific Immunotherapy (ASI), given as adjuvant treatment, improves survival of patients with stage II and III colorectal cancer. Here we report on the effects of adjuvant ASI in patients with Micro Satellite Stable (MSS) versus Micro Satellite Instable (MSI) tumors. From 196 patients with stage II or stage III colorectal cancer who previously participated in the ASI trial published by Vermorken et al. in the Lancet (1999;353:345–50), we collected frozen tumor samples and/or paraffin-embedded tumor material. From this material DNA was extracted and microsatellite status was assessed. Kaplan–Meier curves were plotted to determine survival associations with microsatellite status and treatment group (placebo versus adjuvant ASI treatment). From 196 of the original 256 patients participating in the trial we retrieved good quality archival tumor DNA for further analysis of microsatellite status. We subsequently identified 162 (83%) Micro Satellite Stable tumors and 34 (17%) Micro Satellite Instable tumors. Irrespective of microsatellite status, the current study showed a significant survival benefit for those patients receiving ASI treatment (P = 0.012), as expected based on the results of Vermorken et al. New to this is that irrespective of treatment, patients with MSI tumors showed significantly fewer recurrences than patients with MSS tumors (P = 0.03). Taking both MS status and treatment into account, we found no significant difference in survival between ASI versus placebo treated patients bearing MSI tumors. In contrast to this, we found that patients with MSS tumors benefited from ASI treatment in that ASI treated patients showed significantly improved survival (P < 0.05). It can be concluded that ASI will benefit only patients with MSS tumors, since only they showed significant improved survival upon ASI therapy. For the MSI group there is most likely no benefit of ASI therapy.