In recent years, perioperative chemotherapy has become a hot topic in gastric cancer research. The so-called perioperative chemotherapy includes neoadjuvant chemotherapy and postoperative adjuvant chemotherapy, and neoadjuvant chemotherapy, also known as preoperative chemotherapy, aims to shrink tumors, improve surgical resection rate, control micrometastases, and improve treatment outcomes. In this article, we will review the current status and progress of neoadjuvant chemotherapy. Current status and trends of neoadjuvant chemotherapy for gastric cancer From the recent literature on neoadjuvant chemotherapy for gastric cancer, the author summarizes three major trends of such research, which are described as follows. Expanded therapeutic field The indications for neoadjuvant chemotherapy for gastric cancer are becoming broader, from the initial resectable gastric cancer to the advanced metastatic gastric cancer, including liver metastasis and peritoneal metastasis, thanks to the high efficiency and good tolerability of current chemotherapy drugs. The value of perioperative chemotherapy has been recognized by the academic community from the Cunningham-led MAGIC study. The study randomized 503 resectable adenocarcinomas of the stomach, gastroesophageal junction, and lower esophagus, 250 in the surgery-only group and 253 in the perioperative treatment group, using an ECF regimen (epi-amycin 50 mg/m2 d1, cisplatin 60 mg/m2 d1, and fluorouracil 200 mg/m2 d1-21, repeated every 21 days for three cycles), with the primary study endpoint was the overall survival rate. The results showed no significant difference in the incidence of postoperative complications between the two groups, and perioperative chemotherapy significantly improved patient disease-free survival (HR=0.66) and overall survival (HR=0.75, with five-year survival rates of 36% and 23%, respectively), making this treatment modality the standard of care for progressive gastric cancer in Europe. However, there are two shortcomings in this study: first, the original regimen was not evaluated after preoperative chemotherapy, and the original regimen was continued in postoperative adjuvant chemotherapy; second, the study included adenocarcinoma of the stomach, gastroesophageal junction, and lower esophagus, which are different from each other, and it is inappropriate to fully extrapolate the results of this study to all gastric cancer patients. [The median survival of the neoadjuvant chemotherapy group and the surgery-only group was 20.6 months and 19.9 months, respectively (P=0.02), which may also be supported by the retrospective report of 87 patients with gastric cancer in China, with an effective rate of 51.7% (15/29). Nearly half of the advanced gastric cancers often have peritoneal metastases, which are generally considered to have lost the chance of surgery and have poor results. However, there are many case reports of long-term control and even pCR with S-1-based chemotherapy for peritoneal metastases in Japan recently, which is worth further investigation. Neoadjuvant chemotherapy has also been discussed for patients with liver metastases from gastric cancer, and patients may benefit from a reasonable determination of the indications. Diversification of treatment modalities Perioperative treatment modalities for gastric cancer are currently diversified, including intravenous chemotherapy, combination of radiotherapy and local arterial infusion chemotherapy, especially the first two are most widely used. Intravenous chemotherapy is exemplified by the MAGIC study, while the combination of radiotherapy and chemotherapy is represented by the RTOG9904 study [8]. [Stahl et al. recently reported a comparison between preoperative chemotherapy and preoperative radiotherapy for adenocarcinoma of the gastroesophageal junction. radiotherapy outcomes. The inclusion criteria for this clinical study were locally progressive (uT3-4NXM0) lower esophageal and cardia cancers. The primary endpoint was overall survival time. 354 patients were enrolled in the proposed study, which ended early due to slow enrollment. 126 patients (119 evaluable) were enrolled with similar rates of surgical resection, with numerous patients in the radiotherapy group showing pathologic complete remission ((15.6% vs. 2.0 The radiotherapy group had a high rate of complete pathological remission ((15.6% vs. 2.0%)), a high rate of negative lymph nodes ((64.4% vs. 37.7%)), and a high 3-year overall survival rate (HR=0.67, 47.4% vs. 27.7%), but a slightly higher postoperative mortality rate (10.2% vs. 3.8%; P=0.26). In our unit, neoadjuvant chemotherapy based on oxaliplatin has been introduced in recent years, and the postoperative pathology is in complete remission in about 4%, which is similar to this report. It can be seen that preoperative radiotherapy can also be used for adenocarcinoma of the gastroesophageal junction, but it increases the chance of postoperative complications, including anastomotic leak and abdominal infection. Neoadjuvant interventional chemotherapy has a long history of treating gastric cancer by injecting drugs into the tumor vessels through highly selective arterial cannulae with high local drug concentrations, which can result in significant tumor shrinkage; unfortunately, the results of large sample studies with high credibility are lacking. Individualization of efficacy prediction Individualization of tumor treatment has been an important research direction, and perioperative treatment of gastric cancer also faces the problem of efficacy prediction, which directly affects the decision of treatment. Mansour et al. analyzed 168 gastric cancer patients who received neoadjuvant chemotherapy and R0 resection, and the 3-year disease-specific survival (DSS) rate reached 69% for those with necrotizing degeneration or fibrotic inflammatory changes in the range of histology of 50% or more, and 69% for those with lymph node metastasis, pT3 and above, high histological grade, choroidal nerve invasion, and histological changes