Prognostic and predictive value of DNA mismatch repair status in patients with locally advanced rectal cancer following neoadjuvant therapy.

Abstract

210 Background: DNA mismatch repair deficient (dMMR) is a distinct molecular phenotype of colon cancer related to favorable outcome and resistant to 5-FU based adjuvant chemotherapy, however, little is known about dMMR rectal cancers. We investigated the value of dMMR on prognosis and predicted response to neoadjuvant therapy in rectal cancer patients. Methods: Between January, 2013 and December, 2018, a total of 855 consecutive patients with determined MMR status who underwent neoadjuvant therapy followed by curative surgery for locally advanced rectal cancer were included this retrospective study. Associations of MMR status with clinicopathologic variates and response to neoadjuvant therapy were determined using Chi-square or Fisher Exact tests. Local recurrence-free survival (LRFS) and disease-free survival (DFS) were analyzed using Cox proportional hazard models. Results: In this study population, dMMR was detected in 69 of 855 (8.1%) cases. Patients with dMMR showed similar clinicopathological characteristics including grade of differentiation, location from anal verge, clinical stage, neoadjuvant therapy regimen, pathological stage and postoperative chemotherapy to those who with pMMR, except younger age ( < 65 years, 89.1% vs. 77.7%, P = 0.034) and more mucinous adenocarcinoma in dMMR tumors. MMR status were not predictive for response to neoadjuvant therapy including pCR rate (18.8% vs. 12.9%, P = 0.185), downstaging rate (76.6% vs. 68.9%, P = 0.200) and tumor regression grade 0-1 (31.3% vs. 43.7%, P = 0.052), regardless of chemoradiation or chemotherapy. Multivariable analysis revealed that patients whose tumors had dMMR vs. pMMR had significantly longer DFS (HR = 0.39, 95%CI = 0.18 - 0.83, P = 0.014), but the correlation was not observed for LRFS (HR = 0.81, 95%CI = 0.25 - 2.60, P = 0.724). In the subgroup analysis, dMMR was a statistically significant prognostic factor for DFS only in patients with ypstage II-III (HR = 0.39, 95%CI = 0.17 - 0.88, P = 0.024). Conclusions: dMMR was significantly associated with longer DFS in patients with locally advanced rectal cancer, whereas was not a predictive marker for neoadjuvant therapy.