D2 解剖可改善晚期胃癌患者的疾病特异性生存：意大利胃癌研究组 D1 与 D2 随机对照试验的 15 年随访结果。

D2 dissection improves disease-specific survival in advanced gastric cancer patients: 15-year follow-up results of the Italian Gastric Cancer Study Group D1 versus D2 randomised controlled trial.

机构信息

University of Turin, Department of Oncology, San Luigi University Hospital, Surgical Oncology and Digestive Surgery Unit, Regione Gonzole 10, Orbassano, Turin, 10043, Italy.

出版信息

Eur J Cancer. 2021 Jun;150:10-22. doi: 10.1016/j.ejca.2021.03.031. Epub 2021 Apr 19.

DOI:10.1016/j.ejca.2021.03.031

PMID:33887514

Abstract

BACKGROUND

The extended lymphadenectomy (D2) was recently introduced in several guidelines as the optimal treatment for gastric cancer, based only on the 15-year follow-up results of the Dutch randomised trial, while the British Medical Research Council (MRC) study failed to demonstrate a survival benefit over the more limited D1 dissection. The Italian Gastric Cancer Study Group randomised controlled trial (RCT) was also undertaken to compare D1 versus D2 gastrectomy, and a tendency to improve survival in patients with advanced resectable disease (pT > 1N+) was documented despite negative results in the entire patient population. Now we present the 15-year follow-up results of survival and gastric cancer-related mortality.

METHODS

Between June 1998 and December 2006, eligible patients with gastric cancer who signed the informed consent were randomised at 5 centres to either D1 or D2 gastrectomy. Intraoperative randomisation was implemented centrally by phone call. Primary outcome was overall survival (OS); secondary end-points were disease-specific survival, postoperative morbidity and mortality. Analyses were by intention to treat. Strict quality control measures for surgery, lymph node removal, pathology and patient follow-up were implemented and monitored. Registration number: ISRCTN11154654 (http://www.controlled-trials.com).

FINDINGS

A total of 267 eligible patients were assigned to either D1 (133 patients) or D2 (134) procedure. Median follow-up time was 16.76 years. Analyses were done both in overall patient population and in pT > 1N+. One hundred patients (38.5) were alive without recurrence. OS and disease-specific survival (DSS) were very high in both arms. In overall population, they were not different between D1 and D2 arm (51.3% vs. 46.8% and 65% vs. 67% respectively, p = 0.31 and p = 0.94). DSS was significantly higher after D2 in pT > 1N+ patients (29.4% vs. 51.4%, p = 0.035). OS and DSS were better after D1 in patients older than 70 years (p = 0.003 and p = 0.006). DSS was higher after D1 also in early stages (p = 0.01).

INTERPRETATION

After 15-year follow up, despite no relevant difference in overall population, DSS and gastric cancer-related mortality of patients with advanced disease and lymph node metastases are improved by D2 procedure. Further data available from this trial suggest that D1 procedure should be preferably used in older patients and in early disease. As accurate detection of advanced diseases can be currently provided by adequate preoperative workup in referral centres, D2 procedure should be recommended in these cases.

FUNDING

Piedmont Regional fund for Finalized Healthy Research Project, Application 2003 for data collection.

摘要

背景

在荷兰随机试验的 15 年随访结果基础上，扩展淋巴结清扫术（D2）最近被纳入了几项指南，作为治疗胃癌的最佳选择，而英国医学研究委员会（MRC）的研究未能证明与更有限的 D1 清扫术相比有生存获益。意大利胃癌研究组也进行了随机对照试验（RCT），比较 D1 与 D2 胃切除术，尽管整个患者群体的结果为阴性，但在有进展可切除疾病（pT>1N+）的患者中记录到生存改善的趋势。现在我们报告生存和胃癌相关死亡率的 15 年随访结果。

方法

1998 年 6 月至 2006 年 12 月，符合条件的签署知情同意书的胃癌患者在 5 个中心被随机分为 D1 或 D2 胃切除术组。术中随机化通过中央电话进行。主要结局是总生存（OS）；次要终点是疾病特异性生存、术后发病率和死亡率。分析采用意向治疗。实施并监测了严格的手术、淋巴结清除、病理学和患者随访的质量控制措施。注册号：ISRCTN11154654（http://www.controlled-trials.com）。

结果

共有 267 名符合条件的患者被分配到 D1（133 名患者）或 D2（134 名患者）组。中位随访时间为 16.76 年。分析同时在整体患者人群和 pT>1N+中进行。100 名患者（38.5%）无复发存活。在两组中，OS 和疾病特异性生存（DSS）都非常高。在整体人群中，D1 和 D2 组之间的 OS 和 DSS 无差异（分别为 51.3%对 46.8%和 65%对 67%，p=0.31 和 p=0.94）。在 pT>1N+患者中，D2 后 DSS 显著升高（29.4%对 51.4%，p=0.035）。在>70 岁的患者中，D1 后 OS 和 DSS 更好（p=0.003 和 p=0.006）。在早期阶段，D1 后 DSS 也更高（p=0.01）。