胃癌的外科治疗：随机全国性荷兰 D1D2 试验的 15 年随访结果。

Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial.

机构信息

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Lancet Oncol. 2010 May;11(5):439-49. doi: 10.1016/S1470-2045(10)70070-X. Epub 2010 Apr 19.

DOI:10.1016/S1470-2045(10)70070-X

PMID:20409751

Abstract

BACKGROUND

Historical data and recent studies show that standardised extended (D2) lymphadenectomy leads to better results than standardised limited (D1) lymphadenectomy. Based on these findings, the Dutch D1D2 trial, a nationwide prospectively randomised clinical trial, was undertaken to compare D2 with D1 lymphadenectomy in patients with resectable primary adenocarcinoma of the stomach. The aim of the study was to assess the effect of D2 compared with D1 surgery on disease recurrence and survival in patients treated with curative intent.

METHODS

Between August, 1989, and July, 1993, patients were entered and randomised at 80 participating hospitals by means of a telephone call to the central data centre of the trial. The sequence of randomisation was in blocks of six with stratification for the participating centre. Eligibility criteria were a histologically proven adenocarcinoma of the stomach without evidence of distance metastasis, age younger than 85 years, and adequate physical condition for D1 or D2 lymphadenectomy. Patients were excluded if they had previous or coexisting cancer or had undergone gastrectomy for benign tumours. Strict quality control measures for pathological assessment were implemented and monitored. Analyses were by intention to treat. This study is registered with the NCI trial register, as DUT-KWF-CKVO-8905, EU-90003.

FINDINGS

A total of 1078 patients were entered in the study, of whom 996 were eligible. 711 patients underwent the randomly assigned treatment with curative intent (380 in the D1 group and 331 in the D2 group) and 285 had palliative treatment. Data were collected prospectively and all patients were followed up for a median time of 15.2 years (range 6.9-17.9 years). Analyses were done for the 711 patients treated with curative intent and were according to the allocated treatment group. Of the 711 patients, 174 (25%) were alive, all but one without recurrence. Overall 15-year survival was 21% (82 patients) for the D1 group and 29% (92 patients) for the D2 group (p=0.34). Gastric-cancer-related death rate was significantly higher in the D1 group (48%, 182 patients) compared with the D2 group (37%, 123 patients), whereas death due to other diseases was similar in both groups. Local recurrence was 22% (82 patients) in the D1 group versus 12% (40 patients) in D2, and regional recurrence was 19% (73 patients) in D1 versus 13% (43 patients) in D2. Patients who had the D2 procedure had a significantly higher operative mortality rate than those who had D1 (n=32 [10%] vs n=15 [4%]; 95% CI for the difference 2-9; p=0.004), higher complication rate (n=142 [43%] vs n=94 [25%]; 11-25; p<0.0001), and higher reoperation rate (n=59 [18%] vs n=30 [8%]; 5-15; p=0.00016).

INTERPRETATION

After a median follow-up of 15 years, D2 lymphadenectomy is associated with lower locoregional recurrence and gastric-cancer-related death rates than D1 surgery. The D2 procedure was also associated with significantly higher postoperative mortality, morbidity, and reoperation rates. Because a safer, spleen-preserving D2 resection technique is currently available in high-volume centres, D2 lymphadenectomy is the recommended surgical approach for patients with resectable (curable) gastric cancer.

FUNDING

Dutch Health Insurance Funds Council and The Netherlands Cancer Foundation.

摘要

背景

历史数据和近期研究表明，标准化扩大（D2）淋巴结清扫术比标准化有限（D1）淋巴结清扫术效果更好。基于这些发现，荷兰 D1D2 试验是一项全国范围的前瞻性随机临床试验，旨在比较可切除原发性胃腺癌患者的 D2 与 D1 淋巴结清扫术。该研究的目的是评估 D2 手术与 D1 手术相比对有治愈意图的患者疾病复发和生存的影响。

方法

1989 年 8 月至 1993 年 7 月，80 家参与医院通过电话向试验的中央数据中心随机入组患者。随机序列为 6 个块的分层，分层因素为参与中心。入组标准为组织学证实的无远处转移的胃腺癌，年龄小于 85 岁，以及有足够的身体条件进行 D1 或 D2 淋巴结清扫术。如果患者有既往或并存癌症或因良性肿瘤行胃切除术，则排除在外。实施并监测了严格的病理评估质量控制措施。分析按意向治疗进行。本研究在 NCI 试验注册处注册，登记号为 DUT-KWF-CKVO-8905，EU-90003。

结果

共有 1078 例患者入组该研究，其中 996 例符合条件。711 例患者接受了有治愈意图的随机治疗（D1 组 380 例，D2 组 331 例），285 例患者接受了姑息治疗。数据是前瞻性收集的，所有患者均随访中位数时间为 15.2 年（范围 6.9-17.9 年）。对有治愈意图的 711 例患者进行了分析，并按分配的治疗组进行了分析。711 例患者中，174 例（25%）存活，除 1 例外均无复发。总的 15 年生存率为 D1 组 21%（82 例），D2 组 29%（92 例）（p=0.34）。D1 组胃癌相关死亡率明显高于 D2 组（48%，182 例），而两组其他疾病相关死亡率相似。D1 组局部复发率为 22%（82 例），D2 组为 12%（40 例），D1 组区域复发率为 19%（73 例），D2 组为 13%（43 例）。D2 手术患者的手术死亡率明显高于 D1 手术患者（n=32[10%]与 n=15[4%]；95%置信区间差值为 2-9；p=0.004），并发症发生率更高（n=142[43%]与 n=94[25%]；11-25；p<0.0001），再次手术率更高（n=59[18%]与 n=30[8%]；5-15；p=0.00016）。