Gastric cancer is one of the most common malignant tumors in China, ranking 3rd in both incidence and death of malignant tumors in China. At present, radical surgery is still the only means to cure gastric cancer, but the prognosis of patients with progressive gastric cancer is still poor. According to the 7th edition of the AJCC TNM staging system, the 5-year survival rate of progressive gastric cancer in the United States is about 9.2-45.5%, while the 5-year survival rate of progressive gastric cancer in Japan is 40.4-60.3%, and the recurrence rate of locally progressive gastric cancer after surgery can be 40-60%. Therefore, the perioperative treatment of progressive gastric cancer has become the focus of many clinical studies, aiming to improve patients’ prognosis in combination with surgical treatment. Neoadjuvant chemotherapy is emerging as an important part of the perioperative treatment of progressive gastric cancer and is beginning to occupy a certain position in the treatment of gastric cancer around the world, but the application of neoadjuvant chemotherapy for gastric cancer still lacks certain standardization due to insufficient evaluation of relevant clinical studies and doubtful evidence of evidence-based medicine. Therefore, in the process of neoadjuvant chemotherapy for gastric cancer, it is necessary to consider the combination of chemotherapy regimen and treatment course with the patient’s own condition. If preoperative neoadjuvant chemotherapy affects the surgical decision, then the fundamental purpose of neoadjuvant chemotherapy is lost. Standardized neoadjuvant chemotherapy for gastric cancer requires accurate pre-treatment evaluation and active treatment monitoring and evaluation. Adequate pre-treatment evaluation can maximize the selection of the most appropriate patients for neoadjuvant chemotherapy, while active treatment monitoring and evaluation can select the appropriate treatment cycle for different patients to avoid missing the best time for surgery or increasing the risk of unnecessary chemotherapy and surgery. In this article, we will explain the neoadjuvant chemotherapy for gastric cancer, aiming to promote the standardized and individualized strategies for perioperative treatment of gastric cancer, and present the problems that still exist in this field, in order to promote the progress of gastric cancer research in China. Selection of suitable population for neoadjuvant chemotherapy for gastric cancer According to the US NCCN guidelines and other national guidelines, perfect preoperative endoscopic evaluation and biopsy are the gold standard for gastric cancer diagnosis and determination of its pathological type. The purpose of endoscopic biopsy is to assess the pathological type of tumor through appropriate tissues, and different types of gastric cancer patients have different responsiveness to chemotherapy, which needs to be considered during the implementation of neoadjuvant chemotherapy. For example, hepatocellular adenocarcinoma of the stomach is a rare and specific type of gastric cancer pathology that does not respond well to chemotherapy, and the best treatment strategy is early surgery. However, due to the obvious heterogeneity of gastric cancer, the existing pathological staging of gastric cancer cannot adequately predict the effect of chemotherapy for different types of gastric cancer, which is one of the biggest problems in the perioperative treatment of gastric cancer today. At present, molecular typing of gastric cancer is one of the hot spots of research. Different scholars try to cluster the expression of genes and proteins of different types of gastric cancer to derive different molecular typing of gastric cancer, so as to predict more accurately the responsiveness of different types of gastric cancer to different chemotherapeutic drugs, and then guide clinical work. However, due to the obvious heterogeneity of gastric cancer, the research on molecular staging is still in its initial stage, and it is still necessary to strengthen the translational medicine research to apply its results to clinical practice. Due to the limitations of the pathological staging of gastric cancer, the selection of neoadjuvant chemotherapy population for gastric cancer is mainly based on its pre-treatment clinical stage. At present, clinical staging of gastric cancer is mainly performed by computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound gastroscopy (EUS), and the most commonly used staging system is the 7th edition of AJCC TNM staging of gastric cancer. Based on the MAGIC study and the FNCLCC/FFCD study, the NCCN gastric cancer guidelines recommend preoperative neoadjuvant chemotherapy for patients with resectable gastric cancer at clinical stage T2-4N0-3M0 (Level of Evidence 1), but the guidelines state that because of the low rate of D2 lymph node dissection in these two studies, they are not sufficient to evaluate the effect of preoperative chemotherapy in combination with D2 lymph node dissection in gastric cancer. lymph node dissection for gastric cancer is not sufficient to assess the true prognostic impact of preoperative chemotherapy in combination with D2 lymph node dissection. In addition, since these two studies were conducted mainly in combined esophagogastric cancer, the guideline’s neoadjuvant chemotherapy indication population is mainly inclined to patients with combined esophagogastric cancer. The European ESMO-ESSO-ESTRO guidelines for the management of gastric cancer recommend preoperative neoadjuvant chemotherapy for all operable patients with a clinical stage higher than T1N0 (i.e., stage IB-IIIC). The recommendations for neoadjuvant chemotherapy for gastric cancer are also based on the MAGIC and FNCLCC/FFCD studies, but the guideline is more positive than the NCCN guideline, and its indication population is not limited to patients with combined esophagogastric cancer, while the guideline includes patients with T1N1-3 in the recommended population. It should be noted that since the incidence of gastric cancer in Europe and the United States is lower, the biological behavior of gastric cancer is different from that of Asian populations, and the prevalence of D2 lymph node dissection for gastric cancer is lower than that of Asian countries, the recommendations of the guidelines are only of reference significance and should not be followed blindly. In Japan, neoadjuvant chemotherapy is still not included in the JGCA gastric cancer treatment guidelines. The reason for this is that screening for gastric cancer is widespread in Japan, and early-stage gastric cancer is the predominant type of gastric cancer, with relatively few progressive gastric cancers, and D2 lymph node dissection for gastric cancer is more widespread and has a better prognosis for surgical treatment. prognosis of patients. The incidence of gastric cancer in Korea is similar to that in Japan, but there are still no authoritative multidisciplinary guidelines for the treatment of gastric cancer. The situation in China is special and different from that in Europe, America, Japan and Korea. Due to the large population of gastric cancer in China, the predominance of progressive gastric cancer, and the poor popularity of D2 lymph node dissection for gastric cancer, the appropriate population for neoadjuvant chemotherapy for gastric cancer in China is still controversial. 2011 edition of the Ministry of Health’s gastric cancer treatment standard recommends neoadjuvant chemotherapy for T3/4N1-3M0 locally progressive gastric cancer. Despite the recommendation, there is still a lack of large phase III clinical studies in China to evaluate the best indications for neoadjuvant combined with D2 lymph node dissection for gastric cancer. In addition to pathological type and clinical stage, individual factors of gastric cancer patients are also important factors to be considered in neoadjuvant chemotherapy. Patients who cannot tolerate neoadjuvant chemotherapy, such as those of advanced age, severe comorbidities, or poor general condition, should not follow the guidelines to force chemotherapy to avoid further deterioration of the patient’s general condition and loss of surgical opportunity. Selection of neoadjuvant chemotherapy regimen and course of treatment for gastric cancer The selection of neoadjuvant chemotherapy regimen for gastric cancer should take into account the patient’s physical condition, comorbidities and toxicity of chemotherapy drugs. In clinical application, the two-drug regimen is generally preferred because of its less toxicity. Three-drug regimen can be considered in patients with better general condition and able to tolerate, and the application should also pay attention to timely adjustment of drug dose according to patients’ chemotherapy adverse reactions. The guidelines and ESMO-ESSO-ESTRO guidelines and our guidelines recommend neoadjuvant chemotherapy regimens based on ECF regimens (epirubicin, cisplatin, and fluorouracil), in which both guidelines suggest that fluorouracil can be replaced by capecitabine, and the NCCN guidelines also suggest that cisplatin can be replaced by oxaliplatin, but the European guidelines do not suggest this. Our guidelines recommend a two-drug or three-drug combination chemotherapy regimen, which should not be applied as a single drug, and the chemotherapy regimen recommends ECF and its modified regimen. In practical clinical application, more gastric cancer treatment centers in China choose SOX regimen (S-1, oxaliplatin) and XELOX regimen (capecitabine, oxaliplatin) and other regimens. At present, the international consensus is that neoadjuvant chemotherapy for gastric cancer should be based on fluorouracil, but the specific chemotherapy regimen is still inconclusive and needs to be verified by large clinical studies, therefore, it can be selected according to patients’ painlessness in clinical application. NCCN guidelines recommend 3 cycles of preoperative chemotherapy, European guidelines recommend 6 cycles based on MAGIC study, and China’s treatment standard suggests that the duration of neoadjuvant chemotherapy should not exceed 3 months. Therefore, the most important principle in choosing the chemotherapy course is close monitoring during the treatment period and individualizing the chemotherapy course according to the patient’s tumor changes and efficacy evaluation, so as to bring maximum benefit to the patient while ensuring the radicality of the tumor surgery. Therapeutic monitoring and efficacy evaluation of neoadjuvant chemotherapy for gastric cancer As mentioned above, active therapeutic monitoring plays a pivotal role in neoadjuvant chemotherapy for gastric cancer. The main purpose of active therapeutic monitoring is to assess the tumor responsiveness to chemotherapy and to determine the appropriate course of chemotherapy to determine the optimal timing of surgery. At present, the main imaging methods commonly used in clinical monitoring are CT, MRI and other imaging methods, and imaging evaluation is generally recommended after every 2 cycles of chemotherapy. The main imaging evaluation standards are RECIST 1.1, WHO standards and other standards, among which RECIST 1.1 is the most commonly used. Adequate imaging assessment requires reliable baseline evaluation and the involvement of an experienced imaging physician. If the clinical evaluation is partial remission (PR), continuation of the previous chemotherapy regimen can be considered; if the evaluation is disease progression (PD), active preparation for surgery is required; if the evaluation is stable disease (SD), careful consideration should be given to whether to continue chemotherapy to avoid losing the opportunity for surgery if the disease progresses after continuing chemotherapy. For patients with CR, there is a lack of evidence to determine whether to continue chemotherapy or to proceed to surgery. It is worth noting that the application of the current evaluation criteria in gastric cancer has shortcomings (e.g., the primary lesion of gastric cancer is a non-evaluable lesion) and cannot adequately reflect the postoperative pathological evaluation, and the clinical evaluation criteria for gastric cancer should be urgently studied. In addition to clinical evaluation, pathological evaluation is also an important part of the evaluation of neoadjuvant chemotherapy for gastric cancer. Accurate pathological evaluation can fully judge the effect of preoperative chemotherapy on tumor and provide decision information for the selection of postoperative adjuvant chemotherapy regimen. Currently, the Tumor Regression Grade is commonly used as the pathological evaluation standard of neoadjuvant chemotherapy for gastric cancer. Numerous studies have confirmed the correlation between pathological evaluation and patient survival in patients with gastric cancer treated with neoadjuvant chemotherapy [30-32], but like clinical evaluation criteria, the current pathological evaluation criteria for gastric cancer also have certain shortcomings and need to be further explored. In conclusion The key to standardized neoadjuvant chemotherapy for gastric cancer is to select the appropriate population, chemotherapy regimen, escort with active treatment monitoring, decide on the optimal timing of surgery, and provide a decision basis for postoperative adjuvant chemotherapy based on the pathological evaluation of neoadjuvant chemotherapy after surgery. However, we should also recognize that there are still many issues to be addressed in the implementation of standardized neoadjuvant chemotherapy for gastric cancer: the responsiveness of chemotherapy for gastric cancer of different pathological types, the prognostic significance of neoadjuvant chemotherapy combined with D2 lymph node dissection, the assessment of the optimal neoadjuvant chemotherapy regimen and course for gastric cancer, and the clinical and pathological evaluation of neoadjuvant chemotherapy. Although there are still many problems to be solved, we can foresee that with the emergence of new chemotherapeutic drugs and agents and the rise of targeted therapeutic drugs, neoadjuvant therapy for gastric cancer will play an increasingly important role in the comprehensive treatment of gastric cancer and bring more benefits to patients with progressive gastric cancer.