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.