Emerging issues in multimodality treatment of gastric cancer

In recent years, the treatment of locally advanced resectable gastric cancer has evolved from an exclusively surgical to a multidisciplinary approach including chemotherapy and radiotherapy (RT). Worldwide several evidence-based preoperative and postoperative adjuvant strategies have been implemented in daily clinical practice. The determination of gastric cancer patients that benefit most from certain treatment modalities is a matter of debate. This review covers a comprehensive analysis of outcome and toxicity of clinical trials investigating multimodality treatment for locally advanced resectable gastric cancer to provide insight in patient groups that may benefit from certain treatments. Postoperative chemotherapy as monotherapy and doublet therapy has mainly been evaluated in Asian countries, where its efficacy has been clearly demonstrated. Whereas the added value of postoperative chemotherapy remains to be established in Western patient populations, perioperative doublet and triplet chemotherapy has been shown to improve overall survival (OS) in this part of the world. In addition, postoperative chemoradiotherapy (CRT) as an intensive locoregional treatment has been shown to reduce local recurrence rates and to improve OS. It has been suggested that postoperative CRT may particularly be of additional value in case of a microscopically incomplete R1 resection, a limited lymph node dissection (LND), and/or in case of regional lymph node metastases. Another attractive treatment strategy is preoperative CRT. Phase II trials reported good feasibility and patients’ compliance, low toxicity rates, high R0 resection rates, and promising response rates. No results from randomized controlled trials applying preoperative CRT are available yet, but phase III randomized controlled trials investigating this strategy are currently accruing patients. In gastric cancer treatment, hematological and gastrointestinal toxicity are most frequently encountered in both chemotherapy and CRT either given preoperatively or postoperatively. Toxicity rates are higher with doublet and triplet chemotherapy than with monotherapy. Toxicity rates of the newer CRT regimens are lower than those of the older regimens, and lower than those of combination chemotherapy. For both chemotherapy and CRT, toxicity rates seem lower when treatment is given preoperatively, which probably explains the higher compliance with preoperative treatment. Based on multiple adjuvant preoperative and postoperative treatment regimens that have shown efficacy in patients with locally advanced resectable gastric cancer, all patients should be considered for multimodality treatment. Today, for gastric cancer patients the choice for a specific additional modality can only be based on patient and tumor characteristics regarding preoperative treatment, and surgical and pathological results regarding postoperative treatment. Taken together, preoperative chemotherapy and/or CRT are preferable to postoperative regimens. However, this has to be further confirmed in randomized controlled phase III studies.