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Extended Lymph Node Dissection for Gastric Cancer: Who May Benefit? Final Results of the Randomized Dutch Gastric Cancer Group Trial

The Cancer Institute of New Jersey, New Brunswick, NJ
City of Hope National Medical Center, Duarte, CA

To the Editor:

The authors of the recently updated Dutch gastric cancer trial¹ should be applauded in many respects, but most notably for two reasons: extending a very well-designed and quality controlled study of great clinical relevance to a robust long-term follow-up, and providing insight into the clinical implications by subset analysis. The results continue to support a very obvious conclusion: extended (D2) lymphadenectomy, as performed in this trial, does not lead to an overall survival benefit when compared with limited (Dl) dissection. We caution the informed reader, however, to not fall into any resulting rigor dogmatis by now generally rejecting any extended lymphadenectomy approach for gastric cancer. This request is made for various reasons, most of which the authors have discussed well.

Firstly, increased morbidity and mortality hazards have been linked to D2 dissections in this trial, and for the most part appear to be a result of splenectomy and pancreatectomy performed in roughly a third of patients in the D2 group. Since the inception of the trial, however, several reports have stated the ability to perform adequate D2 dissections rather safely, especially by avoiding splenectomy and pancreatectomy.^2,3 If the operative mortality between the groups had been equal, would a now-obvious D2 survival benefit be the result? The authors should be encouraged to test this aspect by controlling for the imbalances of competing hazards as a result of splenopancreatectomy in form of a propensity score analysis.⁴ Because postgastrectomy mortality appears to depend on hospital volume as well as surgeon experience,⁵ gastrectomies should be considered to take place in centers of excellence anyhow, with D2 dissections to be performed based on the institutional safety record.

Secondly, any anticipated survival benefit as a result of a D2 dissection would be small: Competing hazards that determine extraregional failure, such as diffuse peritoneal relapse or distant metastatic disease, are common in advanced stage disease. Extended regional dissections can sensibly improve only survival for patients with intermediate lymph node involvement when other predictors of distant failure such as serosal involvement and large burden nodal disease are absent.⁶ Does the lack of an obvious survival benefit in any subgroup of the Dutch trial mean that D2 dissections should not be performed at all? No (unless the resulting morbidity is prohibitive), because the lack of power in these subanalyses does not equate into any lack of benefit to a smaller patient subset. In this context, survival differences in the N2 (and to a lesser extent the Nl) subsets can be construed as encouragement for a D2 dissection approach.

Thirdly, there are other putative benefits to extended lymph node dissection: improved locoregional control, as confirmed within this trial, and a more appropriate pathologic staging.⁷ Based on a review of the US-based Surveillance, Epidemiology, and End Results (SEER) database, we found the median lymph node count in patients with intermediate stage gastric cancer undergoing curative intent gastrectomy to be 8, compared with 17 and 30 in the Dutch trial Dl and D2 groups, respectively. Stage subgroup–specific survival depended strongly on the total number of lymph nodes examined and culminated in the highest survival at counts of 40 lymph nodes or more, a strong incentive in favor of extended lymphadenectomy.⁸

Which surgical therapy would the reader choose who had T2N2 gastric cancer? What if that gastric cancer could, but may not, be a T2N2 lesion? We suggest that the best answer probably is gastrectomy with D2 dissection, avoiding splenectomy or pancreatectomy, in a center of excellence with minimal risks associated with the extended dissection. The trial does not refute this option, but its caveats with respect to morbidity and survival impact are valuable points well taken.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Hartgrink HH, Van De Velde CJ, Putter H,et al: Extended lymph node dissection for gastric cancer: Who may benefit? Final results of the randomized Dutch Gastric Cancer Group trial. J Clin Oncol 22:2069-2077, 2004.[Abstract/Free Full Text]

2. Degiuli M, Sasako M, Ponti A, et al: Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the Italian Gastric Cancer Study Group prospective multicenter surgical study. J Clin Oncol 16:1490-1493, 1998[Abstract/Free Full Text]

3. Lewis WG, Edwards P, Barry JD, et al: D2 or not D2? The gastrectomy question. Gastric Cancer 5:29-34, 2002[Medline]

4. Rosenbaum PR, Rubin DB: Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc 79:516-524, 1984[CrossRef]

5. Hannan EL, Radzyner M, Rubin D, et al: The influence of hospital and surgeon volume on in-hospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer. Surgery 131:6-15, 2002[CrossRef][Medline]

6. Schwarz RE, Zagala-Nevarez K: Recurrence patterns after radical gastrectomy for gastric cancer: Prognostic factors and implications for postoperative adjuvant therapy. Ann Surg Oncol 9:394-400, 2002[Abstract/Free Full Text]

7. Brennan MF: Lymph-node dissection for gastric cancer. N Engl J Med 340:956-958, 1999[Free Full Text]

8. Schwarz RE, Schwarz RR, Smith DD: Reliability of gastric cancer staging by numeric lymph node examination: Prognostic impact and postoperative therapy implications. ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, January 22-24, 2004 (abstr 4)

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• In Reply:
  H.H. Hartgrink, H. Putter, and C.J.H. van de Velde
  JCO 2005 23: 5405 [Full Text]

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