Wang Huan-Huan, Yan Yuan-Yuan, Zeng Hong-Yu, Wang Yong, Ni Ke-Min, Yu Xin-Ru, Shi Jin-Ming, Li Hong-Li, Wang Jun-Feng, Yuan Zhi-Yong, Wen Qing-Lian, Zaorsky Nicholas G, Zhang Chun-Ze, Zang Feng-Lin, Meng Mao-Bin
Department of Radiation Oncology and CyberKnife Center, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, China.
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, China.
Front Immunol. 2025 Jul 7;16:1626438. doi: 10.3389/fimmu.2025.1626438. eCollection 2025.
BACKGROUND: For locally advanced rectal cancer (LARC) with a deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H), particularly in patients not eligible for immunotherapy, the optimal treatment remains undetermined. This study was to evaluate the efficacy and safety of surgery, surgery and chemotherapy, surgery and chemoradiotherapy, in patients with LARC harboring dMMR/MSI-H. METHODS: Patients included from three university centers between August 1, 2012 and March 1, 2023, were categorized into three treatment groups: surgery . surgery + chemotherapy . surgery + chemoradiotherapy. The primary endpoint was overall survival (OS), with secondary endpoints of progression-free survival (PFS), local recurrence (LR), distant metastasis (DM), and toxicity. The Kaplan-Meier method was utilized to analyze OS and PFS; competing risk methods were employed to evaluate rates of LR and DM. Adjustments were performed utilizing inverse probability of treatment weighting (IPTW) and overlap weighting (OW) based on propensity score, employing logistic regression model. The Cox proportional hazards model was applied for both univariate and multivariate analyses to assess prognostic factors influencing patient OS and PFS. RESULTS: A total of 119 patients were included, with 45 patients (37.8%) receiving surgery alone, 32 (26.9%) receiving surgery + chemotherapy, and 42 (35.3%) undergoing surgery + chemoradiotherapy. In both the unadjusted cohort and after IPTW and OW adjustments, the surgery alone group (. surgery + chemoradiotherapy) had improved OS, PFS, LR, but no significant differences in DM. However, no statistical difference was found between the surgery . surgery + chemotherapy groups in OS, PFS, and DM, except for significant differences in LR. Similar results were found in both neoadjuvant and adjuvant treatment cohorts. No adverse events of grade 5 occurred. CONCLUSION: This study suggests surgery alone (without chemotherapy and/or radiotherapy) may be an optimal treatment for LARC patients with dMMR/MSI-H, particularly in those who cannot tolerate or access immunotherapy. The results of this study may be used to power a randomized trial for the approaches.
背景：对于错配修复缺陷/微卫星高度不稳定（dMMR/MSI-H）的局部晚期直肠癌（LARC）患者，尤其是那些不适合免疫治疗的患者，最佳治疗方案仍未确定。本研究旨在评估手术、手术联合化疗、手术联合放化疗对dMMR/MSI-H的LARC患者的疗效和安全性。 方法：纳入2012年8月1日至2023年3月1日期间来自三个大学中心的患者，分为三个治疗组：手术组、手术+化疗组、手术+放化疗组。主要终点是总生存期（OS），次要终点是无进展生存期（PFS）、局部复发（LR）、远处转移（DM）和毒性。采用Kaplan-Meier方法分析OS和PFS；采用竞争风险方法评估LR和DM的发生率。利用倾向评分，采用逆概率治疗加权（IPTW）和重叠加权（OW），基于逻辑回归模型进行调整。采用Cox比例风险模型进行单因素和多因素分析，以评估影响患者OS和PFS的预后因素。 结果：共纳入119例患者，其中45例（37.8%）仅接受手术治疗，32例（26.9%）接受手术+化疗，42例（35.3%）接受手术+放化疗。在未调整的队列以及IPTW和OW调整后，单纯手术组（与手术+放化疗组相比）的OS、PFS、LR有所改善，但DM无显著差异。然而，手术组与手术+化疗组在OS、PFS和DM方面未发现统计学差异，除了LR有显著差异。在新辅助和辅助治疗队列中均发现了类似结果。未发生5级不良事件。 结论：本研究表明，单纯手术（不进行化疗和/或放疗）可能是dMMR/MSI-H的LARC患者的最佳治疗方法，尤其是那些无法耐受或无法接受免疫治疗的患者。本研究结果可用于为这些治疗方法开展一项随机试验提供依据。
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