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Originally published as JCO Early Release 10.1200/JCO.2004.03.956 on April 13 2004 © 2004 American Society of Clinical Oncology.
The Debate Is Over; It's Time to Move OnHelen F. Graham Cancer Center, Newark, DE The issue of lymphadenectomy for gastric cancer has been debated in the literature since Noguchi and associates1 proposed that this procedure was important both for accurate tumor staging and for improving survival. I doubt that surgeons would deny that an extended lymphadenectomy improves the accuracy of staging, but whether it contributes to long-term survival has been a matter of continuing debate. Also taken into consideration is the morbidity of an extended lymph node dissection, which more likely occurs with patients who undergo distal pancreatectomy and splenectomy as part of the procedure. In this issue of the Journal of Clinical Oncology (JCO), Hartgrink and associates2 have published the final results of the randomized Dutch Gastric Cancer Trial, which is a follow-up of the original data published in 1994.3 This randomized trial compared the morbidity, mortality, long-term survival, and cumulative risk of relapse of a limited (D1) lymph node dissection to an extended (D2) lymph node dissection for gastric carcinoma. A total of 711 patients were treated with curative intent. The median follow-up for all eligible patients is now 11 years. The authors do an excellent job of describing the D1 and D2 surgical dissections. Standard resection of the spleen and pancreatic tail was only done in proximal gastric tumors to achieve adequate removal of D2 lymph node stations 10 and 11. Morbidity and mortality were statistically significantly higher in the D2 dissection group, but after 11 years of follow-up, there was no overall difference in survival. To the credit of the authors, in-hospital death was defined as death within 30 days of surgery or during the hospital stay, if this was longer than 30 days. This latter definition is often missing from many surgical series that evaluate surgical procedures for mortality. The authors also state that of all subgroups analyzed, only patients with N2 disease may benefit from a D2 dissection, but for this subgroup analysis, no adjustment for multiple testing was applied. Hence, the reader must be cautious about the interpretation of the results of such subset analyses, and these need to be viewed as hypotheses that require validation in future studies. Unfortunately, patients with N2 disease can only be identified after the surgical specimen is examined by the pathologist, and even with modern imaging there is no accurate way of identifying these individuals preoperatively. The authors also conclude that an extended lymph node dissection may be of benefit if morbidity and mortality can be avoided; these were influenced by the extent of lymph node dissection, pancreatectomy, and splenectomy. Unfortunately, the only way to test that hypothesis would be to perform a prospective randomized trial in which the D2 dissection does not include pancreatectomy and splenectomy. Before the readers of JCO irately e-mail me, I am in no way recommending such a trial be performed in the United States. The main reason for performing a pancreatectomy and splenectomy in the D2 dissection was not to compromise an adequate dissection of lymph node stations 10 and 11. However, in this trial, metastases to these lymph nodes conferred a poor prognosis, questioning the importance of the dissection of these lymph node stations, given that the survival benefit was small and morbidity and mortality significantly increased. In my opinion, these final results of the randomized Dutch Gastric Cancer Trial by Hartgrink and associates have ended the debate concerning the extent of lymph node dissection for gastric carcinoma. This was a carefully done, prospective randomized trial, with D1 and D2 dissections clearly defined according to the guidelines of the Japanese Research Society for the study of Gastric Cancer,4 with one of nine referent surgeons who performed the D2 dissections at the local hospitals and adequate division of the lymph node stations further investigated by the local pathologist. Since the technical aspects of the study appear sound, it is very hard to criticize the negative results of this trial on that basis, although I am sure not all will agree. Of course, this further justifies comments made about the results of the Intergroup gastric adjuvant Trial 0116, in which only 10% of the patients had the recommended D2 lymphadenectomy and 54% of the patients had a D0 lymphadenectomy.5 Five-year survival rates for the group that received adjuvant chemotherapy resemble those of the present Dutch Gastric Cancer Trial, in which no adjuvant treatment was given. Hence, it has been stated that the adjuvant chemoradiotherapy simply compensated for inadequate surgery. Although this may be true, it leaves a bitter taste in my mouth, since such inadequate surgery may be the result of surgeons who simply can't technically perform a recommended procedure. In conclusion, as a result of the long-term follow-up of the Dutch Gastric Cancer Trial, the debate over performing a D1 or a D2 lymphadenectomy for gastric cancer should be put to rest. Clinical and scientific research teams of surgical, medical, and radiation oncologists should concentrate their efforts in the areas of training surgical residents and fellows to perform a complete D1 lymphadenectomy, develop new agents for neoadjuvant and adjuvant clinical trials of gastric cancer, and improve radiation techniques. These areas, along with the explosion in genomic medicine, are the future hope for patients with gastric cancer. The debate is over; it's time to move on. Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES 1. Noguchi Y, Imada T, Matsumoto A, et al: Radical surgery for gastric cancer: A review of the Japanese experience. Cancer 64:2053-2062, 1989
2. Hartgrink HH, van de Velde CJH, Putter H, et al: Extended lymph node dissection for gastric cancer: Who may benefit? Final results of the randomized Dutch Gastric Cancer Trial. J Clin Oncol 22:2069-2077, 2004 3. Bunt AMG, Hermans J, Boon MC, et al: Evaluation of the extent of lymphadenectomy in a randomized trial of Western versus Japanese type surgery in gastric cancer. J Clin Oncol 12:417-422, 1994[Abstract] 4. Kajitani T: Japanese Research Society for the Study of Gastric Cancer: The general rules for gastric cancer study in Surgery and Pathology. Jpn J Surg 11:127-145, 1981[CrossRef][Medline]
5. Macdonald JS, Smalley SR, Benedetti J, et al: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725-730, 2001
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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