Chen Lin, Yang Xudong, Zhang Yuanyuan, Liu Jie, Jiang Qixin, Ji Fang, Gao Jinli, Zhou Zhuqing, Wang Hao, Huang Jun, Fu Chuangang
Department of Colorectal Surgery, Department of General Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Pathology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Oncol. 2022 Aug 8;12:920916. doi: 10.3389/fonc.2022.920916. eCollection 2022.
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.
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.
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.
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.
错配修复（MMR）状态对局部晚期直肠癌（LARC）患者在新辅助放化疗背景下生存结局及敏感性的预测作用尚无定论。
招募接受新辅助放化疗（nCRT）的LARC患者的回顾性队列。在调整基线特征后，我们使用倾向评分匹配来减少潜在混杂因素对MMR状态的影响。主要分析以总生存作为更重要的终点。
本研究纳入269例患者。错配修复缺陷（dMMR）患者比错配修复功能正常（pMMR）患者更年轻（58.5%对60.0%，p = 0.0274），体重指数更低（p = 0.0091），分化程度更高（p = 0.0889），直肠癌分期更晚（临床T4或T4b，p = 0.0851；M1，p = 0.0055）。然而，倾向评分匹配后的dMMR患者（p = 0.0013）表现出更好的总生存，即使在M1亚组中也是如此。更重要的是，早期病理降期，尤其是淋巴结病理降期的pMMR患者可获得与dMMR患者相似的预后。
这项回顾性研究的临床意义主要包括两点：（1）我们的研究数据证实，dMMR状态的LARC患者在nCRT后总生存率更高，即使在M1亚组中也是如此。（2）无论dMMR或pMMR，早期淋巴结病理降期的老年和女性患者观察到相似的生存结局。
