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10.1245/ASO.2005.10.908
Annals of Surgical Oncology 12:194-196 (2005)
© 2005 Society of Surgical Oncology
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It Is Still Not the Time to Change Surgical Strategy for Gastric Cancer

Wei-Jei Lee, MD, PhD1

1 En-Chu Kong Hospital, National Taiwan University, Taipei Hsien, Taiwan

Letter to the Editor

It Is Still Not the Time to Change Surgical Strategy for Gastric Cancer

Wei-Jei Lee, MD, PhD1

1 En-Chu Kong Hospital, National Taiwan University, Taipei Hsien, Taiwan

To the Editor:

I read with interest the editorial by Kappas et al.1 The author advocates the application of gastrectomy with D2 lymph node dissection for gastric cancer resection. The recommendation is based on long-term survival findings in the Dutch trial.2 There was a 20% long-term survival rate among N2 patients who had undergone D2 dissection, versus 0% among those who had a D1 resection in the Dutch trial. From these data, the author estimated an overall absolute survival benefit of approximately 6% (30% N2 incidence; 20% N2 survivors) for routine D2 dissection in all patients with curable disease. However, the analysis in the Dutch trial is inappropriate, and the estimation by the author is incorrect.

The classification of D1 and D2 dissection is based on the anatomical level of gastric bed lymph nodes. Theoretically, it is impossible to have N2 staging in D1 dissection. Because the new tumor-node-metastasis staging system adopted lymph node number for the classification of N-stage (node number 1–6 for N1, 7–15 for N2, and >16 for N3), it is possible to have an N2 stage in D1 dissection by this system.3 However, this kind of staging is incorrect, and the patients who underwent D1 dissection would clearly be understaged in N-stage —not in regard to the prevalence of lymph node metastases but in regard to the inadequate dissected area. The survival difference for N2 patients who underwent D1 or D2 dissection should be attributed to stage migration, or the Will Rogers phenomenon, rather than the therapeutic effect of lymphadenectomy.4 For subgroup analysis, the T-stage is more appropriate than N-stage because the T-stages would not be affected by different node dissection areas.5,6 In the Dutch trial, there was no difference in overall long-term survival rates between D1 and D2 dissection or in different T-stage groups. This supports the hypothesis that there is no therapeutic effect of node dissection in gastric cancer.

Therefore, the role of radical lymph node dissection in gastric cancer resection remains controversial. We agree that D2 node dissection, performed by high-volume surgeons, is now safe6,7 and is not necessarily associated with high mortality and morbidity.8,9 However, there is still no evidence to support the therapeutic effect of lymph node dissection in gastric cancer resection. We, surgical oncologists, choose to perform D2 dissection in gastric resection for accurate staging, but we cannot advocate its therapeutic effect.

REFERENCES

  1. Kappas AM, Fatouros M, Roukos DH. Is it time to change surgical strategy for gastric cancer in the United States? Ann Surg Oncol 2004;11:727–30.[Free Full Text]
  2. Hartgrink HH, van-de Velde CJ. Final results of the Dutch D1 versus D2 gastric cancer trial. J Clin Oncol 2003;21:2069– 77.
  3. Lee WJ, Hong RL, Lai IR, et al. Reappraisal the new UICC staging system for gastric cancer: problem in lymph node stage. Hepatogastroenterology 2002;49:860–4.[Medline]
  4. Cady B. Lymph node metastases. Arch Surg 1984;119:1067–72.[Abstract]
  5. Lee WJ. Prognostic relevance of systematic lymph node dissection in gastric carcinoma (letter to the editor). Br J Surg 1994;81:315–6.[Medline]
  6. Lee WJ.. Cancer of the stomach: a review of two hospitals in Korea and Japan (letter to the editor). World J Surg 1995;19:468–9.[Medline]
  7. Lee WJ, Chen TC, Lai IR, et al. Randomized clinical trial of Ligasure versus conventional surgery for extended gastric cancer resection. Br J Surg 2003;90:1493–6.[CrossRef][Medline]
  8. Cushieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resection for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operation Group. Br J Cancer 1999;1:1522–30.
  9. Wu CW, Hsiung CA, Lo SS, et al. Randomized clinical trial of morbidity after D1 and D3 surgery for gastric cancer. Br J Surg 2004;94:283–7.
 

In Reply

Angelos M. Kappas, MD2, Michael Fatouros, MD2 and Dimitrios H. Roukos, MD2

2 Department of Surgery, Ioannina University, School of Medicine, Ioannina, Greece

We thank the authors for their interest in our editorial published in the August issue of the Annals of Surgical Oncology1 and for their letter to the editor. They give us the opportunity to comment again on an extremely complicated topic. Does D2 over D1 dissection provide a survival benefit in patients with gastric cancer? Decades-long debate on this hot topic suggests how difficult and challenging it is to draw conclusions and make recommendations2 about an optimal extent of lymphadenectomy.

Is extended lymphadenectomy for gastric cancer simply of predictive value only, or does it provide therapeutic effects? The authors support the first opinion. Because evidence from randomized controlled trials is lacking with negative the two European randomized controlled trials available,3,4 they based on well-known stage migration phenomenon and different nodal staging systems used in the Dutch trial, support the theory of D2 overtreatment without any true survival advantage for patients with gastric cancer. Is this right, or is a critical analysis needed to draw conclusions?

The following arguments suggest that it is time to move from D1 to D2 gastrectomy under specific safety conditions for patients with localized disease.

  1. Concept: 6 years ago, in contrast to the opinion that D2 does not benefit patients2,3 or improves survival only for stage II tumors or N0 or N1 disease,5 we published for the first time the idea of a pN2 stage-specific survival benefit of D2 surgery.6 For this N2 subgroup, in the Japanese anatomical classification system, the survival rate at 5 years after a D2 gastrectomy was 20%.6 Subsequently, we described this idea and the survival results of our prospective study based on a specific protocol adherent to this idea6 in several articles.7,8,9
  2. Proof of concept: now, the final 11-year survival results of the Dutch trial confirm our hypothesis. The cure rate was 21% after D2, compared with 0% after D1, gastrectomy for N2 patients.10
  3. Revision: Dutch surgeons revised the initial publication of the Dutch trial in the New England Journal of Medicine.3 They conclude now, according to the final results, that D2 dissection is of benefit for N2 patients if the procedure can safely be performed.10
  4. R0 resection: this principal goal of surgery, which is very well established,11 cannot be achieved with limited D1 surgery in N2 patients.12
  5. Recurrence prevention: patients die from recurrence after surgery.11 Leaving the N2 lymph nodes positive because of a D1 gastrectomy in approximately 30% of patients with potentially curable disease,11 we consciously treat these patients with palliative intent. Survival is less than 8 months after incomplete (R1 or R2) resection,13 and it is strongly questionable why surgical oncologists support such a treatment strategy for palliative surgery.
  6. D2 gastrectomy is recommended standard care in Japanese guidelines14 and in recommendations by the Japanese and International Gastric Cancer Associations.

Considering all evidence available about primary tumor biology, its ability to recur after surgery, and new clinical data gained, D2 surgery is the treatment of choice for patients with localized disease. Although circulating cancer cells limit the efficacy of D2 surgery,15 some, but not all, N2 patients, particularly those with serosa-negative cancer, substantially benefit from D2 gastrectomy.16

The survival benefit of patients with N2 disease provided by D2 surgery is 20%.6,10 Whether this rate will reach 40% if a systematic D2/3 or D4 complete lymphadenectomy is performed by highly specialized surgeons and institutions will be clarified by the ongoing Japan Clinical Oncology Group trial.17 D2 surgery should be performed by experienced surgeons, not for staging, but for therapeutic effects. D2 gastrectomy is the only treatment modality currently available able to provide long-term survival after an R0 resection for N2 patients. There are no data, at present, to support the idea that this cure rate can be achieved with D1 surgery combined with chemotherapy, radiotherapy, immunotherapy, targeted molecular therapy, or any other treatment modality.18

REFERENCES

  1. Kappas AM, Fatouros M, Roukos DH. Is it time to change surgical strategy for gastric cancer in the United States? Ann Surg Oncol 2004;11:727–30.[Free Full Text]
  2. Roukos DH. Proof-of-concept changes treatment guidelines for gastric cancer. Gastric Breast Cancer 2004;3:23–6.
  3. Bonnenkamp JJ, Hermans J, Sasako M, van de Velde CJH. Extended lymph-node dissection for gastric cancer. N Engl J Med 1999;340:908–14.[Abstract/Free Full Text]
  4. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resection for gastric cancer: long-term results of the MRC randomised surgical trial. Surgical co-operation group. Br J Cancer 1999;79:1522–30.[CrossRef][Medline]
  5. Siewert JR, Boettcher K, Stein HJ, et al. Relevant prognostic factors in gastric cancer. Ten-year results of the German Gastric Cancer Study. Ann Surg 1998;228:449–61.[CrossRef][Medline]
  6. Roukos DH, Lorenz M, Encke A. Evidence of survival benefit of extended (D2) lymphadenectomy in western patients with gastric cancer based on a new concept: a prospective long-term follow-up study. Surgery 1998;123:573–8.[CrossRef][Medline]
  7. Roukos DH. Extended (D2) lymph node dissection for gastric cancer: do patients benefit (editorial)? Ann Surg Oncol 2000; 7:253–5.[CrossRef][Medline]
  8. Roukos DH. Optimizing lymph node dissection for gastric cancer. Gastric Breast Cancer 2002;1:40–3.
  9. Roukos DH, Kappas AM. Targeting the optimal extent of lymph node dissection for gastric cancer (guest editorial). J Surg Oncol 2002;81:59–62.[CrossRef][Medline]
  10. 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 2004;22:2069–77.[Abstract/Free Full Text]
  11. Roukos DH. Current status and future perspectives in gastric cancer management. Cancer Treat Rev 2000;26:243–55.[CrossRef][Medline]
  12. Roukos DH. Extended lymphadenectomy in gastric cancer: when, for whom and why. Ann R Coll Surg Engl 1998;80:16– 24.[Medline]
  13. Roukos DH, Lorenz M, Karakostas K, Paraschou P, Batsis C, Kappas AM. Pathological serosa and node-based classification accurately predicts gastric-cancer recurrence risk and outcome, and determines potential and limitation of a Japanese- style extensive surgery for Western patients. Br J Cancer 2001;84:1602–9.[CrossRef][Medline]
  14. Nakajima T. Gastric cancer treatment guidelines in Japan. Gastric Cancer 2002;5:1–5.[Medline]
  15. Roukos DH, Kappas AM. Limitations in controlling risk of recurrence after curative surgery for advanced gastric cancer are now well-explained by molecular-based mechanisms (editorial). Ann Surg Oncol 2001;8:620–1.[Free Full Text]
  16. Roukos DH. Early-stage gastric cancer: a highly treatable disease (editorial). Ann Surg Oncol 2004;11:127–9.[Free Full Text]
  17. Sano T, Sasako M, Yamamoto S, et al. Gastric cancer surgery: morbidity and mortality results from a prospective randomized controlled trial comparing D2 and extended para-aortic lymphadenectomy—Japan Clinical Oncology Group Study 9501. J Clin Oncol 2004;22:2767–73.[Abstract/Free Full Text]
  18. Fatouros M, Roukos DH, Agnantis NJ, Kappas AM. Confirming hypothesis-driven surgical concept and comparing potential survival benefit expected by D2 surgery and adjuvant treatment (perspective). Gastric Breast Cancer 2003;2:35–44.



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