Therapy of localized gastric cancer: preoperative and postoperative approaches.

Although gastric cancer remains one of the most commonly diagnosed cancers worldwide, its incidence is declining in many countries. This decline is likely to be due partially to the increased use of refrigeration which has led to increased consumption of fresh foods, and decreased use of salt and pickling as methods of food preservation. The recent recognition of Helicobacter pylori as a cause of peptic ulcer disease and a cocarcinogen have led to treatments that may further decrease its incidence. In the USA, it is estimated that 21600 cases of gastric cancer will be diagnosed in 2002, and it will cause 12400 deaths [1]. Despite this overall decrease, proximal gastric and gastroesophageal junction cancer has been increasing in many countries [2–4]. Recent analyses of patients who sought treatment at M.D. Anderson Cancer Center between 1995 and 1998 showed that 41% of upper gastrointestinal carcinomas involve the esophagogastric junction. Obesity has been associated with proximal gastric cancer in several studies [2–4]. Tobacco use may also play a role. While gastroesophageal reflux disease and Barrett’s metaplasia are associated with esophageal adenocarcinoma, their association with gastric cancer is less clear. Prognostic factors for patients who undergo resection include the type of resection (R), depth of invasion (T), the presence and the number of nodal metastases (N), and the ratio of involved and removed lymph nodes [5, 6]. Outside of Japan, where a screening program is active, gastric cancer is often diagnosed in advanced and unresectable stages. At the time of resection, 75–85% of gastric cancer patients are expected to have nodal involvement and are at high risk for postoperative relapse. The location of cancer in the stomach also has important prognostic implications. The prognosis is worst for diffuse gastric involvement (linitis plastica). Several large studies have shown that proximal gastric cancer has a worse prognosis compared with mid or distal gastric cancer. Our own data show that the adverse effect of gastric cancer localization is limited in patients with local-regional disease [7]. In addition to these clinical pathological factors, molecular markers have also been found to be of prognostic value. Expression of PDGF-α, Her-2/neu, TGF-β and EGFR has been associated with inferior survival [8–12]. In addition, high TS and ERCC1 expression has been linked to poor prognosis among patients receiving fluoropyrimidineand platinumbased chemotherapy [13–15]. Despite advances in cancer therapy, the survival duration of gastric cancer patients who have undergone surgical resection remains dismal in the West. In a recent report from the American College of Surgeons and the American Cancer Society, the 5-year survival rates for patients with resected stage II, IIIa, IIIb and IV gastric cancer were 34%, 20%, 8% and 7% [16]. To improve the outcome of these patients, numerous clinical trials of adjuvant chemotherapy have been carried out in the past decades. Recently, trials of newer approaches, such as combined modality chemoradiotherapy and preoperative therapy, have also been conducted. Here, we summarize key randomized adjuvant therapy for gastric carcinoma and review preoperative strategies.