Fast track — ArticlesSurgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial
Introduction
After several decades of debate on what the optimum surgical treatment of gastric cancer should be, it is now possible to treat patients using evidence-based principles established by well designed and conducted studies. Adequate surgery, the only treatment known to offer cure, is still the cornerstone of gastric-cancer treatment; however, local regional control remains an issue. In western Europe and the USA, optimum local control and survival seemed to be reached with surgery as a single-modality treatment, based mainly on two large European trials, the Dutch Gastric Cancer Trial (DGCT)1 and the UK Medical Research Council (MRC) randomised trial.2 In both trials, standardised extended (D2) lymphadenectomy did not improve survival, and was associated with significantly higher morbidity and mortality compared with standardised limited (D1) lymphadenectomy. The unfavourable outcomes were mostly associated with pancreatico-splenectomy, which was an integral part of the D2 resection in both trials. In 2004, results from a study by Degiuli and colleagues3 suggested a survival benefit after pancreas-preserving D2 resections, and in 2006, a Taiwanese single-institution trial4 found that extended lymph-node dissection (D2) led to better results (no postoperative mortality) than D1 lymphadenectomy. More extended resection (D2 plus para-aortic nodal dissection) was not found to be better than D2 resections in Japanese patients.5
As a result of the INT0116 trial,6 a combination of surgery and postoperative chemoradiotherapy became the standard treatment for curable gastric cancer in the USA. In this trial, fluorouracil plus leucovorin given concomitantly with 45 Gy radiation after potentially curative surgery improved 3-year survival from 41% to 50%, compared with surgery alone. In Europe, following the results of the UK MAGIC trial,7 perioperative chemotherapy with the ECF (epirubicin, cisplatin, and fluorouracil) became the new treatment standard for gastric cancer. The MAGIC trial found that perioperative systemic chemotherapy improved 5-year survival from 23% to 36%, compared with surgery alone. Randomised controlled trials in Japanese patients have shown significant improvement in overall survival with postoperative adjuvant chemotherapy with S-1 (an orally active combination of tegafur, gimeracil, and oteracil) after D2 dissection.8 Therefore, S-1 after D2 surgery is becoming the standard treatment for patients with gastric cancer in Japan.
Early results from the DGCT showed significantly higher postoperative morbidity and mortality in the D2 group compared with the D1 group.9 With the 5-year follow-up results showing no significant survival benefit in the D2 group, a conclusion was drawn that D2 resection could not be advised in patients with curable gastric cancer.10 However, 11-year follow-up data showed better survival results in exploratory analyses in patients with stage II and IIIa disease who had D2 compared with D1 resections.1 The current report is the 15-year follow-up data of the DGCT.
Section snippets
Patients
The DGCT was approved by the medical ethics committees of the Leiden University Medical Center and all participating hospitals. Written or oral informed consent was obtained according to the principles of the institution. 80 hospitals participated in the trial. Eligible patients had histologically proven adenocarcinoma of the stomach without evidence of distance metastasis, were younger than 85 years, and were in adequate physical condition for D1 or D2 lymphadenectomy. Patients were excluded
Results
Between August, 1989, and July, 1993, 1078 patients with gastric adenocarcinoma were entered and randomised (539 to each group) in the DGCT. 996 patients met the eligibility criteria and were randomly assigned to have a D1 or D2 lymph-node dissection. Because of peritoneal, hepatic, or distant lymph-node metastasis or locally irresectable disease, 285 patients (29%) underwent palliative surgery without a formal lymph-node dissection, according to the discretion of the surgeon. Of these 285
Discussion
Our findings based on 15-year follow-up data of the DGCT show that D2 lymphadenectomy is associated with lower locoregional recurrence and fewer gastric-cancer-related deaths than D1. The drawback of a D2 resection is its association with significantly higher postoperative mortality and morbidity. However, at the time of the trial, resection of the spleen and pancreatic tail were regarded as necessary for adequate removal of D2 lymph-node stations 10 and 11 in proximal tumours, and in D1 in
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