Annals of Oncology 19 (Supplement 5): v99–v102, 2008 doi:10.1093/annonc/mdn320 symposium article Perioperative or postoperative therapy for resectable gastric cancer? R. Labianca 1 , P. Sburlati 2 , A. Quadri 1 & M. C. Garassino 2 1 Oncology Department Ospedali Riuniti, Bergamo; 2 Oncology Department Ospedale Fatebenefratelli e Oftalmico, Milano, Italy introduction The long-term survival of gastric cancer patients is determined by the stage of the disease and therefore, by the tumor extension beyond the gastric wall and by the nodal involvement. Tumor confined to the mucosa and submucosa (T1–T2 N0 M0) has a 5-year survival of at least 70%, while invasion into the serosa increases the risk of lymph node metastases with a proportionate reduction of the 5-year survival rate, reported in Western series to be 20–30% [1–3]. To date, radical primary tumor resection is the main standard of care for patients with potentially resectable gastric cancer, which represents 50% of all new diagnoses; however, the prognosis of these patients remains poor, ranging between 15% and 35% at 5 years, due to locoregional failure and distant metastases [4]. For many decades the way a multimodal approach and an adequate surgical technique could improve the outcome of the patients only treated with surgery has been under debate and several topics have been under investigation. extension of lymphadenectomy Curative gastrectomy for gastric cancer should include the complete removal of the primary tumor and of its regional lymph nodes, achieving correct staging and better local control. The approach to lymph node dissection is different between Asian and Western surgeons. Several Asian studies suggested a survival advantage with extended lymphadenectomy in gastric cancer patients. Systematic node dissection (D2) is actually the standardized procedure in Asia, where it shows postoperative morbidity and mortality rates lower than in Western series with higher rates of post-surgical survival [5]. There is no definitive evidence showing the superiority of extensive lymphadenectomy and its impact on overall survival is still not demonstrated in randomized controlled trials. A large European randomized trial comparing D1 and D2 dissection with a long-term follow-up failed to demonstrate a relevant difference in survival and relapse rate of the two procedures [6]. Similar results were found by the Medical Research Council and later reviewed in 2003 by the Cochrane group [7, 8]. Pancreatectomy and splenectomy, performed as part of the D2 dissection to remove lymph nodes at the splenic hilus and along the splenic artery, are associated with an increased risk of morbidity and mortality, and no clear evidence of overall survival difference is demonstrated. Therefore, radical surgery possibly avoiding resection of the pancreas and the spleen is currently the standard procedure in Eastern countries [6]. While the West is still debating whether D2 is better than D1 dissection, Asians are discussing the possible role of a more extensive lymphadenectomy including para-aortic nodes. The Japan Oncology Group conducted a randomized controlled trial to compare the standard D2 and D2+ para-aortic nodal dissection; they confirmed the safety of gastrectomy with D2 lymphadenectomy performed by specialized surgeons. This procedure could be used safely in patients with low operative risk. More extensive surgery did not increase the major operative complications but did lead to higher morbidity mainly due to other minor complications [9]. Additional strategies including pre/postoperative chemoradiotherapy to improve locoregional control as well as overall survival are warranted. postoperative chemotherapy The disappointing prognosis of gastric cancer patients after radical surgery justifies the worldwide effort to develop effective strategies to improve outcome in these patients. For more than 40 years several 5-fluorouracil (FU) combinations, effective in metastatic gastric cancer, have been evaluated in the adjuvant setting; the majority of these trials did not reveal a clear long-term benefit for postoperative chemotherapy. In Asian countries, where gastric cancer is a common disease, several studies have been performed in the adjuvant setting, showing a survival benefit. However, these studies induced criticisms: some of them were not randomized trials, sometimes they did not include surgical controls and they usually included patients with stage I–IV cancer, not commonly evaluated together in Western clinical trials [10]. While Asian studies were often positive, the majority of the Western studies failed to demonstrate a positive influence of postoperative systemic treatments. However, Western studies also have their criticisms: some of them are underpowered to detect any difference in overall survival and use suboptimal chemotherapy regimens. The efficacy of adjuvant chemotherapy was also widely analyzed in several meta-analyses, all showing a slight benefit symposium article ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org