Medical Oncology Department, Leon Berard Center, Lyon, France.
Gastroenterology and Hepatology Department, Poitiers University Hospital, University of Poitiers, Poitiers, France.
Int J Cancer. 2023 Oct 1;153(7):1376-1385. doi: 10.1002/ijc.34636. Epub 2023 Jul 5.
About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR.
约 5%的转移性结直肠癌（mCRC）患者存在微卫星不稳定性（MSI）/错配修复系统缺陷（dMMR）。虽然转移性切除术已知可改善 mCRC 的总生存期和无进展生存期，但在特定的 dMMR/MSI mCRC 患者中缺乏具体结果。我们的研究旨在描述 dMMR/MSI mCRC 患者的转移性切除术结果，描述组织学反应，并评估病理完全缓解（pCR）率。我们回顾性分析了 2010 年 1 月至 2021 年 6 月期间，17 家法国中心的 88 例连续接受 dMMR/MSI mCRC 手术治疗的患者的数据。主要结局是评估肿瘤消退分级（TRG）0 定义的 pCR 率。次要终点包括无复发生存期（RFS）和总生存期（OS），并探讨 TRG 作为 RFS 和 OS 的预测因素。在接受手术的 88 例患者中，有 81 例患者在新辅助治疗后进行了 109 次转移切除术[化疗±靶向治疗（CTT）：69 例，85.2%；免疫治疗（ICI）：12 例，14.8%]，13 例（16.1%）患者达到了 pCR。在这些患者中，接受 CTT 治疗的患者（N=7）pCR 率为 10.2%，接受 ICI 治疗的患者（N=6）pCR 率为 50.0%。影像学反应不能预测 TRG。中位随访 57.9 个月（IQR 34.2-81.6），中位 RFS 为 20.2 个月（15.4-未达到），中位 OS 未达到。主要病理反应（TRG0+TRG1）与较长的 RFS显著相关（HR 0.12，95%CI 0.03-0.55；P=0.006）。dMMR/MSI mCRC 患者接受新辅助治疗后的 16.1%pCR 率与 pMMR/MSS mCRC 报告的率一致。免疫治疗的 pCR 率优于化疗±靶向治疗。需要进一步的前瞻性试验来验证免疫治疗作为可切除/潜在可切除 dMMR/MSI mCRC 的新辅助治疗，并确定 pCR 的预测因素。
