Annals of Surgical Oncology

, Volume 20, Issue 7, pp 2328–2338 | Cite as

Long-Term Survival After Gastrectomy for Cancer in Randomized, Controlled Oncological Trials: Comparison between West and East

  • Sheraz R. Markar
  • Alan Karthikesalingam
  • Daniel Jackson
  • George B. HannaEmail author
Gastrointestinal Oncology



The presence of mixed evidence about the value of lymphadenectomy in gastric cancer surgery coupled with the difference in patients’ demographics and tumor stage between the West and East have doubted the needs to standardize surgical techniques in Western clinical practice. The purpose of this study was to compare survival rates between the West and East following gastrectomy in randomized, controlled, oncological trials with appropriate adjustment for confounding variables.


Systematic search revealed 25 trials that have randomization into surgery and chemotherapy versus surgery alone between 1995 and 2012 (n = 7 (East) and n = 18 (West)). End points were 5-year survival and cancer recurrence.


There was association between gastrectomy performed in the East and improved 5-year survival (pooled odds ratio (OR) 4.83; 95 % confidence interval (CI) 3.27–7.12) and reduced cancer recurrence (pooled OR 0.33; 95 % CI 0.2–0.54). Association of improved 5-year survival with surgery in the East remained when meta-regression adjusted for the effect of age, sex, chemotherapy, tumor depth and nodal status, and gastrectomy type. Association of reduced cancer recurrence also persisted with meta-regression adjusting for age, chemotherapy, nodal status, and gastrectomy type. However, when adjustment for the percentage of patients with tumor depth T1 or 2 was made statistical significance was lost.


This analysis shows association between gastrectomy performed in Eastern countries and improved survival. The known difference in surgical techniques between the East and the West is one potential unexamined variable that may be responsible in part for such discrepancy in outcomes.


Gastric Cancer Tumor Depth Japan Clinical Oncology Group Oncological Trial Compare Survival Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.




Conflict of interest



  1. 1.
    Blot WJ, Devesa SS, Kneller RW, et al. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991;265:1287–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Noguchi Y, Imada T, Matsumoto A, et al. Radical surgery for gastric cancer. A review of the Japanese experience. Cancer. 1989;64:2053–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Griffin SM. Gastric cancer in the East: same disease, different patient. Br J Surg. 2005;92:1055–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Park DJ, Lee HJ, Kim HH, et al. Predictors of operative morbidity and mortality in gastric cancer surgery. Br J Surg. 2005;92:1099–102.PubMedCrossRefGoogle Scholar
  6. 6.
    Sasako M, Sano T, Yamamoto S, et al. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med. 2008;359:453–62.PubMedCrossRefGoogle Scholar
  7. 7.
    Bollschweiler E, Boettcher K, Hoelscher AH, et al. Is the prognosis for Japanese and German patients with gastric cancer really different? Cancer. 1993;71:2918–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Noguchi Y, Yoshikawa T, Tsuburaya A, et al. Is gastric carcinoma different between Japan and the United States? Cancer. 2000;89:2237–46.PubMedCrossRefGoogle Scholar
  9. 9.
    Strong VE, Song KY, Park CH, et al. Comparison of gastric cancer survival following R0 resection in the United States and Korea using an internationally validated nomogram. Ann Surg. 2010;251:640–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer. 1999;79:1522–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Bonenkamp JJ, Hermans J, Sasako M, et al. Extended lymph-node dissection for gastric cancer. N Engl J Med. 1999;340:908–14.PubMedCrossRefGoogle Scholar
  12. 12.
    Songun I, Putter H, Kranenbarg EM, et al. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11:439–49.PubMedCrossRefGoogle Scholar
  13. 13.
    Bunt AM, Hermans J, van de Velde CJ, et al. Lymph node retrieval in a randomized trial on western-type versus Japanese-type surgery in gastric cancer. J Clin Oncol. 1996;14:2289–94.PubMedGoogle Scholar
  14. 14.
    Degiuli M, Sasako M, Calgaro M, et al. Morbidity and mortality after D1 and D2 gastrectomy for cancer: interim analysis of the Italian Gastric Cancer Study Group (IGCSG) randomised surgical trial. Eur J Surg Oncol. 2004;30:303–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Wu CW, Hsiung CA, Lo SS, et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 2006;7:309–15.PubMedCrossRefGoogle Scholar
  16. 16.
    Siewert JR, Kestlmeier R, Busch R, et al. Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases. Br J Surg. 1996;83:1144–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Sue-Ling HM, Johnston D, Martin IG, et al. Gastric cancer: a curable disease in Britain. BMJ. 1993;307:591–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Anderson O, Ni Z, Moller H, et al. Hospital volume and survival in oesophagectomy and gastrectomy for cancer. Eur J Cancer. 2011;37:747–53.Google Scholar
  19. 19.
    Van Cutsem E, Dicato M, Geva R, et al. The diagnosis and management of gastric cancer: expert discussion and recommendations from the 12th ESMO/World Congress on Gastrointestinal Cancer, Barcelona 2010. Ann Oncol. 2011;22(Suppl 5):v1–9.PubMedCrossRefGoogle Scholar
  20. 20.
    McCulloch P, Niita ME, Kazi H, et al. Gastrectomy with extended lymphadenectomy for primary treatment of gastric cancer. Br J Surg. 2005;92:5–13.PubMedCrossRefGoogle Scholar
  21. 21.
    Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.PubMedCrossRefGoogle Scholar
  22. 22.
    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. 2001;345:725–30.PubMedCrossRefGoogle Scholar
  23. 23.
    Nakajima T, Kinoshita T, Nashimoto A, et al. Randomized controlled trial of adjuvant uracil-tegafur versus surgery along for serosa-negative, locally advanced gastric cancer. Br J Surg. 2007;94:1468–76.PubMedCrossRefGoogle Scholar
  24. 24.
    Nakajima T, Nashimoto A, Kitamura M, et al. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Lancet. 1999;354:273–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Nashimoto A, Nakajima T, Furukawa H, et al. Randomized trial of adjuvant chemotherapy with mitomycin, fluorouracil, and cytosine arabinoside following by oral fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology group 9206–1. J Clin Oncol. 2003;12:2282–7.CrossRefGoogle Scholar
  26. 26.
    Miyashiro I, Furukawa H, Sasako M, et al. Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2. Gastric Cancer. 2011;14:212–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29:4387–93.PubMedCrossRefGoogle Scholar
  28. 28.
    Yu W, Whang I, Chung HY, et al. Indications for early postoperative intraperitoneal chemotherapy of advanced gastric cancer: results of prospective randomized trial. World J Surg. 2011;25:985–90.CrossRefGoogle Scholar
  29. 29.
    Nio Y, Koike M, Omori H, et al. A randomized consent design trial of neoadjuvant chemotherapy with tegafur plus uracil (UFT) for gastric cancer—a single institute study. Anticancer Res. 2004;24:1879–87.PubMedGoogle Scholar
  30. 30.
    Bajetta E, Buzzoni R, Mariani L, et al. Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group. Ann Oncol. 2002;13:299–307.PubMedCrossRefGoogle Scholar
  31. 31.
    Bouche O, Ychou M, Burtin P, et al. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol. 2005;16:1488–97.PubMedCrossRefGoogle Scholar
  32. 32.
    Chipponi J, Huguier M, Pezet D, et al. Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer. Am J Surg. 2004;187:440–5.PubMedCrossRefGoogle Scholar
  33. 33.
    De Vita F, Giuliani F, Orditura M, et al. Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study). Ann Oncol. 2007;18:1354–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Di Costanzo F, Gasperoni S, Manzione L, et al. Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC. J Natl Cancer Inst. 2008;100:388–98.PubMedCrossRefGoogle Scholar
  35. 35.
    Kulig J, Kolodziejczyk P, Sierzega M, et al. Adjuvant chemotherapy with etoposide, adriamycin and cisplatin compared with surgery along in the treatment of gastric cancer: a phase III randomized, multicenter clinical trial. Oncology. 2010;78:54–61.PubMedCrossRefGoogle Scholar
  36. 36.
    Lise M, Marchet A, Sahmoud T, et al. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in respectable gastric cancer. J Clin Oncol. 1995;13:2757–63.PubMedGoogle Scholar
  37. 37.
    Macdonald S, Fleming TR, Peterson RF, et al. Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alones for patients with locally advance gastric adenocarcinoma: A Southwest Oncology Group Study. Ann Surg Oncol. 1995;2:488–94.PubMedCrossRefGoogle Scholar
  38. 38.
    Neri B, Cini G, Andreoli F, et al. Randomized trial of adjuvant chemotherapy versus control after curative resection of gastric cancer: 5-year followup. Br J Cancer. 2001;84:878–80.PubMedCrossRefGoogle Scholar
  39. 39.
    Nitti D, Wils J, Guimaraes Dos Santos J, et al. Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI Group and ICCG. Ann Oncol. 2005;17:262–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Popiela T, Kulig J, Czupryna A, et al. Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer. Gastric Cancer. 2004;7:240–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Tsavaris NB, Tendas K, Kosmidis P, et al. A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin with no treatment in operable gastric cancer. Chemotherapy. 1996;42:220–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.PubMedCrossRefGoogle Scholar
  43. 43.
    Hartgrink HH, van de Velde CJH, Putter H, et al. Neo-adjuvant chemotherapy for operable gastric cancer: long term results of the Dutch randomised FAMTX trial. Eur J Surg Oncol. 2004;30:643–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer Randomized trial 40954. J Clin Oncol. 2010;28:5210–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999;18:2693–708.PubMedCrossRefGoogle Scholar
  46. 46.
    Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted? Stat Med. 2002;21:1559–73.PubMedCrossRefGoogle Scholar
  47. 47.
    White IR. Multivariate random-effects meta regression: updates to mvmeta. Stata J. 2011;11:255–70.Google Scholar
  48. 48.
    Higgins JP, Thompson SG. Quantifying heterogeneity in meta-analysis. Stata Med. 2002; 21: 1539–58.CrossRefGoogle Scholar
  49. 49.
    Oh SJ, Hyung WJ, Li C, et al. Effect of being overweight on postoperative morbidity and long-term surgical outcomes in proximal gastric carcinoma. J Gastroenterol Hepatol. 2009;24:475–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Kulig J, Sierzega M, Kolodziejczyk P, et al. Implications of overweight in gastric cancer: a multicenter study in a Western patient population. Eur J Surg Oncol. 2010;36:969–76.PubMedCrossRefGoogle Scholar
  51. 51.
    Peters CJ, Rees JR, Hardwick RH, et al. A 4-gene signature predicts survival of patients with resected adenocarcinoma of the esophagus, junction, and gastric cardia. Gastroenterology. 2010;139:1995-2004.PubMedCrossRefGoogle Scholar
  52. 52.
    McCulloch PG, Ochiai A, O’Dowd GM, et al. Comparison of the molecular genetics of c-erb-B2 and p53 expression in stomach cancer in Britain and Japan. Cancer. 1995;75:920-5.PubMedCrossRefGoogle Scholar
  53. 53.
    Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.PubMedCrossRefGoogle Scholar
  54. 54.
    Seevaratnam R, Bocicariu A, Cardoso R, et al. A meta-analysis of D1 versus D2 lymph node dissection. Gastric Cancer. 15;60–9.Google Scholar
  55. 55.
    Lewis WG, Edwards P, Barry JD, et al. D2 or not D2? The gastrectomy question. Gastric Cancer. 5:29–34.Google Scholar

Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Sheraz R. Markar
    • 1
  • Alan Karthikesalingam
    • 2
  • Daniel Jackson
    • 3
  • George B. Hanna
    • 1
    Email author
  1. 1.Department of Surgery and CancerSt. Mary’s Hospital, Imperial CollegeLondonUK
  2. 2.Department of Outcome ResearchSt. George’s Vascular Institute, St. George’s HospitalLondonUK
  3. 3.MRC Biostatistic UnitCambridgeUK

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