Survival results of a multicentre phase II study to evaluate D2 gastrectomy for gastric cancer

Abstract

Curative resection is the treatment of choice for potentially curable gastric cancer. Two major Western studies in the 1990s failed to show a benefit from D2 dissection. They showed extremely high postoperative mortality after D2 dissection, and were criticised for the potential inadequacy of the pretrial training in the new technique of D2 dissection, prior to the phase III studies being initiated. The inclusion of pancreatectomy and splenectomy in D2 dissection was associated with increased morbidity and mortality. Following these results, we started a phase II trial to evaluate the safety and efficacy of pancreas-preserving D2 dissection. The results of this trial regarding the safety of pancreas preserving D2 dissection were published in 1998. In this paper, we present the survival results of this phase II trial to confirm the rationale of carrying out a phase III study comparing D1 vs D2 dissection for curable gastric cancer. Italian patients with histologically proven gastric adenocarcinoma were registered in the Italian Gastric Cancer Study Group Multicenter trial. The study was carried out based on the General Rules of the Japanese Research Society for Gastric Cancer. A strict quality control system was achieved by a supervising surgeon of the reference centre who had stayed at the National Cancer Center Hospital, Tokyo, to learn the standard D2 gastrectomy and the postoperative management. The standard procedure entailed removal of the first and second tier lymph nodes. During total gastrectomy, the pancreas was preserved according to the Maruyama technique. Complete follow-up was available to death or 5 years in 100% of patients and the median follow-up time was 4.38 years. Out of 297 consecutive patients registered, 191 patients were enrolled in the study between May 1994 and December 1996. The overall morbidity rate was 20.9%. The postoperative in-hospital mortality was 3.1%. The overall 5-year survival rate among all eligible patients was 55%. Survival was strictly related to stage, depth of wall invasion, lymph node involvement and type of gastrectomy (distal vs total). Our results suggest a survival benefit for pancreas-preserving D2 dissection in Italian patients with gastric cancer if performed in experienced centres. A phase III trial among exclusively experienced centres is urgently needed.

International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus

“…In the German gastric cancer study, a prognostic advantage of the D2-LAD was detected for the Union for International Cancer Control (UICC) stage II and IIIA disease [7,16]. Two recent prospective observational studies confirm the results of the non-randomized studies of the 1990s [28,29], and randomized studies from the Netherlands and the UK confirm earlier work that found lower rates of loco-regional recurrences after D2-LAD [30]. In two randomized trials with high proportions of splenectomy/pancreatectomy, a prognostic advantage after D2-LAD could not be detected [30,31].…”

Gastric carcinoma in China: Current status and future perspectives (Review)

“…In europe and the UsA, D2 and more aggressive lymphadenectomies are not advocated, while D0 lymphadenectomy is thought to be insufficient; therefore, D1 lymphadenectomy is preferred (9,10). Previously, a phase II clinical trial of D2 resection by the Italian gastric cancer study group showed a morbidity rate of 20.9% and a postoperative mortality rate of 3.0%, which are similar to the rates for D1 dissections in both the Dgcg (7) and Mrc (8) trials, suggesting that D2 lymphadenectomy results in fewer complications in european as well as in Asian countries (11).…”

Sentinel lymph node biopsy in gastric cancer: Possible applications and limits

“…Nodal involvement in gastric cancer depends on the depth of cancer infiltration across the layers of the stomach (TNM staging): it occurs in 2-18% of T1 and in about 50% of T2 tumours. The surgical treatment of gastric cancer, in particular concerning the extent of LN dissection, varies among centres, but in many countries, for example Italy and Germany, the standard approach includes first and second level lymphadenectomy, independent of the evidence of LN metastases or the depth of cancer infiltration [3,4]. This means that in many patients lymphadenectomy is performed unnecessarily.…”