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. 2022 Aug 8:12:920916.
doi: 10.3389/fonc.2022.920916. eCollection 2022.

Survival outcomes analysis according to mismatch repair status in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy

Lin Chen  1 , Xudong Yang  1 , Yuanyuan Zhang  1 , Jie Liu  1 , Qixin Jiang  1 , Fang Ji  1 , Jinli Gao  2 , Zhuqing Zhou  1 , Hao Wang  3 , Jun Huang  4 , Chuangang Fu  1
Affiliations

Survival outcomes analysis according to mismatch repair status in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy

Lin Chen et al. Front Oncol. .

Abstract

Background: The predictive role of mismatch repair (MMR) status for survival outcomes and sensitivity in neoadjuvant chemoradiotherapy settings for patients with locally advanced rectal cancer (LARC) has been inconclusive.

Methods: A retrospective cohort of patients with LARC treated with neoadjuvant chemoradiotherapy (nCRT) was recruited. After adjusting for baseline characteristics, we used propensity score matching to reduce the effect of potential confounding factors on MMR status. The primary analysis was based on overall survival as the more important endpoint.

Results: This study included 269 patients. Patients with defective MMR (dMMR) were younger (58.5% vs. 60.0%, p=0.0274) and had lower body mass indices (p=0.0091), higher differentiation grades (p=0.0889), and more advanced rectal cancers (clinical T4 or T4b, p=0.0851; M1, p=0.0055) than those with proficient MMR (pMMR). However, propensity score-matched patients with dMMR (p=0.0013) exhibited superior overall survival, even in the M1 subgroup. More importantly, patients with proficient MMR who undergo early pathological downstaging, especially lymph node pathological downstaging, can achieve a prognosis similar to that of patients with dMMR.

Conclusion: The clinical significance of this retrospective study mainly includes two points: (1) Data from our study confirmed that LARC patients with dMMR status had better overall survival rates after nCRT, even in the M1 subgroup. (2) Similar survival outcomes were observed in older and female patients with early lymph node pathological downstaging, regardless of dMMR or pMMR.

Keywords: locally advanced rectal cancer; mismatch repair status; neoadjuvant chemoradiotherapy; retrospective cohort study; survival outcome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier curves for recurrence-free survival (A) and overall survival (B) according to MMR status in the whole unmatched patients. MMR denotes mismatch repair, dMMRdefective MMR; pMMRproficientMMR.
Figure 2
Figure 2
Kaplan-Meier curves for recurrence-free survival (A) and overall survival (B) according to MMR status in the propensity score matched subset patients. MMR denotes mismatch repair, dMMRdefective MMR; pMMRproficientMMR.
Figure 3
Figure 3
Kaplan-Meier curves for recurrence-free survival (A) and overall survival (B) according to MMR status in the TRG downstage subset patients. MMR denotes mismatch repair, dMMRdefective MMR; pMMRproficientMMR; TRG, tumor regression grade.
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