Department of Colorectal Surgery, Haut-Lévèque Hospital, Pessac, CHU Bordeaux, France.
Département de Chirurgie Oncologique, ICM Val d'Aurelle, Montpellier, France.
Lancet. 2017 Jul 29;390(10093):469-479. doi: 10.1016/S0140-6736(17)31056-5. Epub 2017 Jun 7.
Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy, to potentially avoid morbidity and side-effects of rectal excision. The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer.
We did a prospective, randomised, open-label, multicentre, phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer. Patients aged 18 years and older with stage T2T3 lower rectal carcinoma, of maximum size 4 cm, who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour ≤2 cm) were centrally randomly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery. Randomisation, which was done via the internet, was not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was required if tumour stage was ypT2-3. The primary endpoint was a composite outcome of death, recurrence, morbidity, and side-effects at 2 years after surgery, to show superiority of local excision over total mesorectal excision in the modified intention-to-treat (ITT) population (expected proportions of patients having at least one event were 25% vs 60% for superiority). This trial was registered with ClinicalTrials.gov, number NCT00427375.
From March 1, 2007, to Sept 24, 2012, 186 patients received chemoradiotherapy and were enrolled in the study. 148 good clinical responders were randomly assigned to treatment, three were excluded (because they had metastatic disease, tumour >8 cm from anal verge, and withdrew consent), and 145 were analysed: 74 in the local excision group and 71 in the total mesorectal excision group. In the local excision group, 26 patients had a completion total mesorectal excision. At 2 years in the modified ITT population, one or more events from the composite primary outcome occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62-2·86; p=0·43). In the modified ITT analysis, there was no difference between the groups in all components of the composite outcome, and superiority was not shown for local excision over total mesorectal excision.
We failed to show superiority of local excision over total mesorectal excision, because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects, and compromised the potential advantages of local excision. Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy.
National Cancer Institute of France, Sanofi, Roche Pharma.
对于新辅助化疗后临床反应良好的直肠癌患者，器官保存是一种概念，旨在避免直肠切除的发病率和副作用。本研究的目的是比较低位直肠癌患者在接受放化疗后良好反应时的局部切除和全直肠系膜切除术。
我们在法国 15 个三级中心进行了一项前瞻性、随机、开放标签、多中心、3 期临床试验，这些中心都是直肠癌治疗方面的专家。年龄在 18 岁及以上、最大尺寸为 4cm 的 T2T3 低位直肠癌患者，对新辅助放化疗有良好的临床反应（残留肿瘤≤2cm），在手术前由外科医生通过中央随机分配接受局部切除或全直肠系膜切除术。随机分配通过互联网进行，不进行分层，使用大小为 8 的置换块。在局部切除组，如果肿瘤分期为 ypT2-3，则需要进行全直肠系膜切除的完成。主要终点是手术后 2 年内死亡、复发、发病率和副作用的复合结局，以显示局部切除在改良意向治疗（ITT）人群中的优越性（预期至少有一个事件的患者比例分别为 25%和 60%）。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT00427375。
从 2007 年 3 月 1 日到 2012 年 9 月 24 日，186 名患者接受了放化疗，并被纳入了这项研究。148 名临床反应良好的患者被随机分配治疗，其中 3 名被排除（因为他们患有转移性疾病、肿瘤距肛门缘>8cm 和撤回同意），145 名被分析：74 名在局部切除组，71 名在全直肠系膜切除组。在局部切除组中，26 名患者接受了全直肠系膜切除的完成。在改良 ITT 人群中，2 年时，局部切除组 73 名患者中有 41 名（56%）发生了主要复合结局的一个或多个事件，全直肠系膜切除组 69 名患者中有 33 名（48%）发生了主要复合结局的一个或多个事件（比值比 1.33，95%CI 0.62-2.86；p=0.43）。在改良 ITT 分析中，两组在复合结局的所有组成部分均无差异，局部切除组并不优于全直肠系膜切除组。
我们未能证明局部切除优于全直肠系膜切除，因为局部切除组的许多患者接受了全直肠系膜切除的完成，这可能增加了发病率和副作用，并损害了局部切除的潜在优势。更好的患者选择以避免不必要的全直肠系膜切除可以改善这种策略。
法国国家癌症研究所、赛诺菲、罗氏制药。
