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Primary surgery with gastrectomy and, if feasible, with extended D2 node dissection is the current standard treatment of operable gastric cancer. However, it is widely accepted that without adjuvant systemic treatment, the high relapse and death rates can hardly be improved. Despite research efforts, neither a chemotherapeutic regimen nor the timing of chemotherapy administration (i.e., before or after surgery) has been standardized. For the first time now, the MAGIC trial provides level I evidence for a survival benefit of perioperative chemotherapy over surgery alone in patients with localized gastric cancer. However, this study raises several questions: given that it was designed to assess an overall benefit and not a stage-specific survival benefit, it remains unknown as to which subgroups (II, IIIA or IIIB) mostly benefit from a perioperative regimen of epirubicin, cisplatin, and infused fluorouracil (ECF). Another key question is the impact of the MAGIC study in daily clinical practice. As several treatment options become available, uncertainty of oncologists for selecting an optimal adjuvant chemotherapy between perioperative, neoadjuvant and postoperative setting increases. Gastric cancer is an aggressive malignancy with nearly 700,000 deaths annually (the second leading cause of cancer death) and a prevalence of around 930,000 new patients annually worldwide. Even the most appropriate local therapy, as an extensive D2/ D3 surgery, which increases the rate of a true complete surgical pathologic R0 resection, is associated with a substantial proportion of recurrence and death. Particularly in patients with advanced serosa-positive, node-positive gastric cancer, the 10year survival rate ranges between 10% and, at best, 30%. Overall, less than 30% of Western patients are cured with local therapy alone as an R0 resection. Systemic adjuvant treatment is required for survival improvements. The biological and clinical heterogeneity of gastric cancer represents a major challenge of current and future molecular and clinical research. 14,15 Clinical data provide differential outcomes among patients with same TNM stage (I, II or III) and treatment and thus there is a clear requirement for tailoring adjuvant systemic therapy in treating specific subgroups of patients. Clinical models converted into a software program using conventional clinicopathologic prognostic factors have been developed and validated, but both these nomograms and the surgical pathologic TNM staging system have two major limitations: First, they cannot identify patients with local disease who could spare the toxic effects of unnecessary chemotherapy. Second, these conventional models cannot predict the response to certain chemotherapeutic regimens among patients with systemic disease who truly require adjuvant systemic treatment to reduce disease relapse and death rates. In contrast to the proven efficacy of adjuvant cytotoxic chemotherapy in other adenocarcinomas including colorectal, lung and breast cancer, no conclusive data exist for gastric cancer. Many phase III clinical trials have explored this approach in Received November 30, 2006; accepted January 12, 2007; published online: July 26, 2007. Address correspondence and reprint requests to: Dimitrios H. Roukos; E-mail: droukos@cc.uoi.gr, info@gastricbreastcancer.com

Level I Evidence in Support of Perioperative Chemotherapy for Operable Gastric Cancer: Sufficient for Wide Clinical Use?