Do microsatellite instability (MSI) and deficient mismatch repair (dMMR) affect the pathologic complete response (pCR) in patients with rectal cancer who received neoadjuvant treatment?

Recently, individualized approaches for the treatment of locally advanced rectal cancers (RC) have been introduced to determine the most beneficial one for boosting the tumor response and assessing the response more accurately. However, despite each patient and tumor have different molecular features, the studies at the molecular level are very limited. In this study, examining the clinical factors which are predictive of pathologic complete response (pCR), helping to determine a treatment program for the management of patients with locally advanced RC, and evaluating the relation between regression grade and MMR-MSI were aimed. 341 RC cases who had undergone surgery were included and divided into three groups according to their response to neoadjuvant treatment. The following parameters were analyzed for all patients: age at diagnosis, sex, tumor location, tumor differentiation, TNM stage, histological subtype, CEA (mean: < 5 ng/ml) level, lymphovascular-neural invasion, presence of mucinous subtype, grade, MMR, and MSI statuses. 147 patients (43.2%) had no response (group 1), 141 patients (41.3%) had an intermediate response (group 2), and 53 patients (15.5%) had a complete response (group 3). Neoadjuvant chemoradiotherapy was used in all of the patients with the same protocol. Multivariate analysis revealed that clinical T stage (p: 0.099) and MMR (p: 0.048) were the parameters which were significantly associated with pCR. Since MMR and MSI statuses were found to affect pCR, more careful patient selection for “watch and wait” protocol and further studies on molecular structures of the tumors for individualized therapies are required.