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直肠癌的放化疗联合局部切除保肛治疗:GRECCAR 2 随机试验的 5 年结果。

Organ preservation with chemoradiotherapy plus local excision for rectal cancer: 5-year results of the GRECCAR 2 randomised trial.

机构信息

Department of Colorectal Surgery, Haut-Lévèque Hospital, CHU Bordeaux, France.

Radiotherapy Department, Haut-Lévèque Hospital, CHU Bordeaux, France.

出版信息

Lancet Gastroenterol Hepatol. 2020 May;5(5):465-474. doi: 10.1016/S2468-1253(19)30410-8. Epub 2020 Feb 7.


DOI:10.1016/S2468-1253(19)30410-8
PMID:32043980
Abstract

BACKGROUND: GRECCAR 2 was the first multicentre, randomised trial to compare local excision with total mesorectal excision in downstaged low rectal cancer. Encouraging oncological results were noted at 3 years' follow-up but needed to be corroborated with longer follow-up. In this study, we aimed to report the 5-year oncological outcomes, including local recurrence, metastatic disease, and survival. METHODS: Patients age 18 years and older with T2T3 low rectal cancer, of maximum size 4 cm, who were clinically good responders after chemoradiotherapy (residual tumour ≤2 cm) were randomly assigned before surgery to either local excision or total mesorectal excision. Randomisation was centralised and not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was performed if pathological tumour stage was ypT2-3. The primary objective of this study was to assess the 5-year oncological outcomes of local recurrence, metastatic disease, disease-free survival, overall survival, and cancer-specific mortality, which were the secondary endpoints of GRECCAR 2. We used Kaplan-Meier estimates and Cox modelling to estimate and compare recurrence and survival in modified intention-to-treat and as-treated populations. This trial was registered with ClinicalTrials.gov, number NCT00427375. FINDINGS: Between March 1, 2007, and Sept 24, 2012, 148 patients who were good clinical responders were randomly assigned to treatment, three patients were excluded after randomisation (because they had metastatic disease, tumour >8 cm from anal verge, or withdrew consent), leaving 145 for analysis: 74 in the local excision group and 71 in the total mesorectal excision group. Median follow-up was 60 months (IQR 58-60) in the local excision group and 60 months (57-60) in the total mesorectal excision group. 23 patients died and five were lost to follow-up. In the local excision group, 26 had a completion total mesorectal excision for ypT2-3 tumour. In the modified intention-to-treat analysis, there was no difference between the local excision and total mesorectal excision groups in 5-year local recurrence (7% [95% CI 3-16] vs 7% [3-16]; adjusted hazard ratio [HR] 0·71 [95% CI 0·19-2·58]; p=0·60), metastatic disease (18% [CI 11-30] vs 19% [11-31]; 0·86 [0·36-2·06]; p=0·73), overall survival (84% [73-91] vs 82% [71-90]; 0·92 [0·38-2·22]; p=0·85), disease-free survival (70% [58-79] vs 72% [60-82]; 0·87 [0·44-1·72]; p=0·68), or cancer-specific mortality (7% [3-17] vs 10% [5-20]; 0·65 [0·17-2·49]; p=0·53). INTERPRETATION: The 5-year results of this multicentre randomised trial corroborate the 3-year results, providing no evidence of difference in oncological outcomes between local excision and total mesorectal excision. Local excision can be proposed in selected patients having a small T2T3 low rectal cancer with a good clinical response after chemoradiotherapy. FUNDING: National Cancer Institute of France.

摘要

背景:GRECCAR 2 是第一项比较低位直肠癌降期后局部切除与全直肠系膜切除的多中心随机试验。在 3 年随访时观察到了令人鼓舞的肿瘤学结果,但需要更长时间的随访来证实。在这项研究中,我们旨在报告 5 年的肿瘤学结果,包括局部复发、转移疾病和生存。

方法:入组标准为年龄 18 岁及以上、最大肿瘤尺寸为 4cm 的 T2T3 低位直肠癌患者,在放化疗后临床反应良好(残留肿瘤 ≤2cm),在术前随机分为局部切除组或全直肠系膜切除组。随机分组采用中央化、非分层、大小为 8 的随机分组。在局部切除组中,如果病理肿瘤分期为 ypT2-3,则进行全直肠系膜切除的补救性治疗。本研究的主要目的是评估局部复发、转移疾病、无病生存、总生存和癌症特异性死亡率的 5 年肿瘤学结果,这些是 GRECCAR 2 的次要终点。我们使用 Kaplan-Meier 估计和 Cox 模型来估计和比较改良意向治疗和实际治疗人群的复发和生存情况。这项试验在 ClinicalTrials.gov 注册,编号为 NCT00427375。

结果:2007 年 3 月 1 日至 2012 年 9 月 24 日期间,共有 148 名临床反应良好的患者被随机分配治疗,3 名患者在随机分组后被排除(因为他们患有转移疾病、肿瘤距肛门缘 >8cm 或撤回同意),留下 145 名患者进行分析:局部切除组 74 名,全直肠系膜切除组 71 名。局部切除组的中位随访时间为 60 个月(IQR 58-60),全直肠系膜切除组为 60 个月(57-60)。23 名患者死亡,5 名患者失访。在局部切除组中,26 名患者因 ypT2-3 肿瘤接受了全直肠系膜切除的补救性治疗。在改良意向治疗分析中,局部切除组和全直肠系膜切除组在 5 年局部复发(7%[95%CI 3-16]vs 7%[3-16];调整后的危险比[HR]0.71[95%CI 0.19-2.58];p=0.60)、转移疾病(18%[CI 11-30]vs 19%[11-31];0.86[0.36-2.06];p=0.73)、总生存(84%[73-91]vs 82%[71-90];0.92[0.38-2.22];p=0.85)、无病生存(70%[58-79]vs 72%[60-82];0.87[0.44-1.72];p=0.68)或癌症特异性死亡率(7%[3-17]vs 10%[5-20];0.65[0.17-2.49];p=0.53)方面均无差异。

结论:这项多中心随机试验的 5 年结果证实了 3 年结果,没有证据表明局部切除与全直肠系膜切除在肿瘤学结果方面存在差异。对于在放化疗后具有良好临床反应的小 T2T3 低位直肠癌患者,可以选择局部切除。

资金来源:法国国家癌症研究所。

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