Abstract
Prior reports have indicated that defective mismatch repair (MMR) has a favorable impact on outcome in colorectal cancer patients treated with surgery, immunotherapy, or adjuvant chemotherapy. However, the impact of MMR status on response to neoadjuvant radiotherapy in rectal cancer is not well understood. Here we report that dMMR was associated with improved disease-free survival (DFS) (P = 0.034) in patients receiving neoadjuvant chemotherapy (NCT). Patients with dMMR tumors who received neoadjuvant chemoradiotherapy (NCRT) achieved significantly worse DFS (P = 0.026) than those treated with NCT. Conversely, NCRT improved DFS (P = 0.043) in patients with pMMR tumors, especially for stage III disease with improved DFS (P = 0.02). The presence of dMMR was associated with better prognosis in rectal cancer patients treated with NCT. NCT benefited patients with dMMR tumors; while NCRT benefited patients with stage III disease and pMMR tumors. Patients stratified by MMR status may provide a more tailored approach to rectal cancer neoadjuvant therapy.
Highlights
Deficient mismatch repair or microsatellite instability (MSI) is one of the well-established molecular biomarkers in colorectal cancer (CRC) and MSI testing has been recommended for all CRC patients according to the National Comprehensive Cancer Network (NCCN) guidelines[1] due to its aid in dictating management[2,3]
Immunotherapy alone or combined with conventional therapy are being rapidly developed for Deficient mismatch repair (dMMR) CRCs16, the predictive value of MMR status in neoadjuvant radiotherapy (NRT) remains undefined in rectal cancer
For patients with dMMR tumors, the percentage of stage III patients in neoadjuvant chemotherapy (NCT) group was higher than Neoadjuvant chemoradiotherapy (NCRT) group
Summary
Deficient mismatch repair (dMMR) or microsatellite instability (MSI) is one of the well-established molecular biomarkers in colorectal cancer (CRC) and MSI testing has been recommended for all CRC patients according to the National Comprehensive Cancer Network (NCCN) guidelines[1] due to its aid in dictating management[2,3]. The exploration of different avenues of neoadjuvant therapy, such as the omission of NRT or selective NRT before chemotherapy and total mesorectal excision, is currently under investigation[14,15] (PROSPECT clinical trial, etc.). For these patients receiving NRT or not are determined on an individual basis, and there is a tremendous demand for predictive biomarkers to select optimal patients who can benefit the most from NRT. We aimed to investigate the association of MMR status with survival and response to neoadjuvant chemo(radio)therapy
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