Mismatch Repair System Deficiency is associated with response to neoadjuvant chemoradiation in locally advanced rectal cancer

Abstract Purpose Defective mismatch repair system (MMR) has been shown to have a favorable impact on outcome in colorectal cancer patients treated with surgery or immunotherapy, adjuvant chemotherapy being discouraged unless there is nodal involvement. Its impact on radiosensitivity is unknown in rectal cancer patients. Methods and Materials Patients treated for locally advanced rectal cancer between 2000 and 2016 were studied. Reported points included age, sex, clinical and radiological tumor stages at diagnosis, modalities of neoadjuvant treatment, post-treatment pathological staging, tumor regression score, and local, distant relapse-free, and overall survivals. An inverse probability of treatment weighting (IPTW) propensity score analysis was performed to evaluate the association of MMR proficiency on surgical and clinical outcomes. Results Among the 296 patients included, 23 (7.8%) had defective MMR (dMMR). Median follow-up was 43.0 months (IQR: 27.9-66.7). dMMR patients were significantly younger than the others. After IPTW propensity score matching, dMMR patients had higher pathological downstaging rate (p Conclusions MMR deficiency was associated with significant tumor downstaging after neoadjuvant chemoradiation as well with increase recurrence-free survival. dMMR patients may have more radiosensitive tumors.