Recent Strategies for Treating Stage IV Gastric Cancer: Roles of Palliative Gastrectomy, Chemotherapy, and Radiotherapy

Recently, many strategies have been reported for the effective treatment of gastric cancer. However, the strategy for treating stage IV gastric cancer remains controversial. Conducting a prospective phase III study in stage IV cancer patients is difficult because of heterogeneous performance status, age, and degree of cancer metastasis or extension. Due to poor prognosis, the variance in physical status, and severe symptoms, it is important to determine the optimal strategy for treating each individual stage IV patient. In the past decade, many reports have addressed topics related to stage IV gastric cancer: the 7th Union for International Cancer Control (UICC) TNM staging system has altered its stage IV classification; new chemotherapy regimens have been developed through the randomized ECF for advanced and locally advanced esophagogastric cancer (REAL)-II, S-1 plus cisplatin versus S-1 in RCT in the treatment for stomach cancer (SPIRITS), trastuzumab for gastric cancer (ToGA), ramucirumab monotherapy for previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD), and ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW) trials; and the survival efficacy of palliative gastrectomy has been denied by the reductive gastrectomy for advanced tumor in three Asian countries (REGATTA) trial. Current strategies for treating stage IV patients can be roughly divided into the following five categories: palliative gastrectomy, chemotherapy, radiotherapy, gastric stent, or bypass. In this article, we review recent publications and guidelines along with above categories in the light of individual symptoms and prognosis. Abbreviations: APC: argon plasma coagulation; AVAGAST: anti-angiogenic antibody bevacizumab, the avastin in gastric cancer; BSC: best supportive care; CF: cisplatin and fluorouracil; CRP: C-reactive protein; DCF: docetaxel, cisplatin, and 5-FU; FISH: fluorescent in-situ hybridization; GJ: gastrojejunostomy; GPS: Glasgow Prognostic Score; HER: human epidermal growth factor receptor; HR: hazard ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PS: performance status; QOL: quality of life; RAINBOW: ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma; RCTs: randomized controlled trials; REAL: randomized ECF for advanced and locally advanced esophagogastric cancer; REGARD: ramucirumab monotherapy for previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma; REGATTA: reductive gastrectomy for advanced tumor in three Asian countries; SEER: Surveillance Epidemiology and End Results; SEMS: self-expandable metal stents; SPIRITS: S-1 plus cisplatin versus S-1 in RCT in the treatment for stomach cancer; ToGA: trastuzumab for gastric cancer; TTP: time-to-progression; VEGFR: vascular endothelial growth factor receptor.