Prognostic and predictive roles of DNA mismatch repair status in colon cancer patients treated with oxaliplatin-based chemotherapy: a retrospective study.

Abstract

This study aims to evaluated the prognostic and predictive roles of DNA mismatch repair status in colon cancer patients treated with oxaliplatin-based chemotherapy. From 2005 to 2008, patients who underwent curative surgical resection for high-risk stage II or stage III colon cancer were recruited in this study. These patients had been received oxaliplatin-based chemotherapy. A total 324 patients were included (41.7% at stage II and 58.3% at stage III), and 59 patients (18.2%) exhibited mismatch repair-deficient (dMMR). The prognostic analysis revealed an increase in disease-free survival (DFS) for dMMR patients versus proficient MMR (pMMR) patients (81.4% versus 64.2%, P = 0.009), and overall survival (OS) (86.4% versus 69.1%, P = 0.004). Among the 82 patients who did not receive adjuvant therapy, the 5-year DFS was significantly higher in patients with dMMR (81.3%) than in patients with pMMR (49.7%, P = 0.040). In the multivariate models, dMMR was independently associated with improved DFS (HR = 2.171, 95% CI: 1.108 - 4.253, P = 0.024) and OS (HR = 2.521, 95% CI: 1.190 - 5.339, P = 0.016). In the predictive analysis, it was observed that the benefit of treatment significantly differed according to the DNA MMR status (P = 0.020). Compared with surgery alone, oxaliplatin-based adjuvant chemotherapy improved the 5-year DFS (69.9% versus 56.2%, P = 0.024) among patients with pMMR in the multivariable analysis (HR = 0.794, 95% CI = 0.646 - 0.976, P = 0.029). In contrast, the oxaliplatin-based chemotherapy in the group with dMMR had no benefit in DFS (83.1% versus 81.8%, HR 1.040, 95% CI: 0.276 - 3.922, P = 0.954). Patients with dMMR colon cancer are associated with improved survival rates, compared with pMMR colon cancer. MMR status is an independent prognostic biomarker for DFS in patients with high-risk stage II and stage III colon cancer. Oxaliplatin-based adjuvant chemotherapy mainly benefits patients with pMMR, but may not benefit patients with tumors exhibiting dMMR.