Clinical impact of microsatellite instability in patients with stage II and III gastric cancer: Results from the CLASSIC trial.

Abstract

4022 Background: The clinical implications of microsatellite instability (MSI) in gastric cancer are unclear. We investigated the usefulness of MSI status as a predictor of prognosis and responsiveness to adjuvant chemotherapy in patients with stage II and III gastric cancer. Methods: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five mononucleotide markers were used to assess tumor MSI status. Results: Of 592 specimens, 36 (6.1%) were MSI-high (MSI-H), whereas others were MSI-low or microsatellite-stable (MSS). Among 286 patients not treated with adjuvant therapy, those with MSI-H tumors had a better 5-year disease-free survival rate than did those with MSI-low/MSS tumors (hazard ratio adjusted by age, sex, tumor grade, disease stage, tumor location: 0.244 [95% confidence interval, 0.069–0.867]; p = 0.0292). Among 306 patients who received adjuvant chemotherapy, MSI-H status did not correlate with better disease-free survival (adjusted hazard ratio: 0.561 [95% confidence interval, 0.190–1.654]; p = 0.2946). Benefits from adjuvant chemotherapy differed by MSI status; although adjuvant chemotherapy improved disease-free survival among patients with MSI-low/MSS (adjusted hazard ratio: 0.634 [95% confidence interval, 0.485–0.828]; p = 0.0008), no benefit was observed in the MSI-H group (adjusted hazard ratio: 1.877 [95% confidence interval, 0.284–12.390]; p = 0.5130). Conclusions: Among patients with stage II and III gastric cancer, a MSI-H status correlated with a favorable prognosis, and adjuvant chemotherapy benefited those with MSI-L/MSS tumors but not those with MSI-H tumors.