Mismatch repair system deficiency is associated with chemoradiotherapy resistance in locally advanced rectal adenocarcinoma patients

Abstract

Background and Objectives Previous studies have concluded that colorectal cancer patients with deficient mismatch repair (dMMR) usually have a good prognosis. However, some studies have suggested that the prognosis of rectal cancer patients with dMMR appears to be worse. Our aim was to investigate chemoradiotherapy resistance in dMMR rectal tumors. Methods A retrospective study of 217 patients with locally advanced rectal adenocarcinoma treated with chemoradiotherapy and total mesorectal excision surgery was conducted using immunohistochemistry to determine MMR status and propensity score matching models to reduce potential confounders. Kaplan–Meier analysis, log‐rank test, and Cox regression models were used to assess overall survival (OS) and disease‐free survival (DFS) in patient subgroups. Results The 3‐year DFS rates were 77.1% and 56.7% in the pMMR and dMMR groups, respectively. The pMMR group had significantly better DFS than the dMMR group (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.10–3.91; p = 0.019). However, there was no significant difference in OS between the two groups (45.7 [interquartile range, IQR], 39.3–72.1] vs. 47.5 [IQR, 29.5–72.1]) (HR, 1.39; 95% CI, 0.70–2.77; p = 0.35). Neither OS nor DFS was significantly different between the neoadjuvant chemoradiotherapy and postoperative chemoradiotherapy groups. Conclusion Locally advanced dMMR rectal adenocarcinoma exhibits greater chemoradiotherapy resistance than pMMR.

Microsatellite instability in rectal cancer: what does it mean? A study of two randomized trials and a systematic review of the literature

“…Yang et al 25 . and Ni et al 26 . were considered outliers after analysis of the 1.5 × IQR rule to find outliers or prevalence of MSI.…”

“…The total number of MSI cases in these studies (including our own) was 1220 (out of 16,526 rectal cancer patients), with an overall prevalence of 6.7% (interquartile range [IQR] limits À7.44, 18.88, standard error 1.19%). Yang et al 25 and Ni et al 26 were considered outliers after analysis of the 1.5 9 IQR rule to find outliers or prevalence of MSI. In Figure 1, the prevalence of MSI cases per study is shown.…”

Management of Rectal Cancer in Lynch Syndrome: Balancing Risk Reduction and Quality of Life

“…In a recent propensity-matched analysis, there was no difference seen in the rate of downstaging for MSI-H (54.5%) and MSS (50%) rectal cancer after nCRT. 25 In general, if there is bulky disease or nodal involvement, we recommend nCRT, and do not offer an IPAA. Choices after nCRT include either TPC and EI or LAR.…”

“…In a recent propensity-matched analysis, there was no difference seen in the rate of downstaging for MSI-H (54.5%) and MSS (50%) rectal cancer after nCRT. 25…”

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review

“…A study by de Rosa et al showed the high effectiveness of neoadjuvant CRT in a series of 62 rectal cancer patients [44]. Other studies, however, displayed no association with CRT efficacy [45], or even resistance to CRT [46]. It is anticipated that forthcoming clinical trials will reveal the role of MMR status when tested together with TIL-density as an important tool to guide immuno-radiotherapy combinations for rectal cancer.…”