Since mass screening for gastric cancer is not yet widespread in China, most patients are already locally advanced or advanced when they are detected. For patients with locally advanced stage, sometimes surgery is performed directly, sometimes a dozen chemotherapy is recommended before considering surgery, and sometimes post-operative chemotherapy is recommended. In the following, we will introduce the perioperative (preoperative + intraoperative + postoperative) treatment of gastric cancer and related considerations. What is chemotherapy? Chemotherapy is a treatment method that uses chemical drugs to directly kill tumor cells, or inhibit the growth of tumor cells, or promote the differentiation of tumor cells to a normal state. It is a kind of “systemic” treatment, and the so-called “systemic” means that chemotherapy can treat the primary lesions of tumor origin, lesions metastasized to other organs, or tiny metastases that exist in the blood and cannot be detected by doctors. There are many kinds of chemotherapeutic drugs and many ways to use them. There are many types of chemotherapeutic drugs and many ways to treat stomach cancer, such as paclitaxel and docetaxel, fluorouracil, capecitabine, tegeo, cisplatin, epirubicin, irinotecan, etc. Most of these drugs are administered intravenously. Most of these drugs are given intravenously, some are given orally, and intravenous drugs can also be given through the chest or abdominal cavity. Doctors sometimes combine different drugs of this type and sometimes apply a particular drug alone, depending on the patient’s condition and body type. Why do some patients who can have surgery need chemotherapy first? What are the precautions? Since mass screening of gastric cancer is not yet popular in our country, no more than 15% of cases can be diagnosed at the early stage of gastric cancer occurrence, and most patients are already at locally advanced or late stage when gastric cancer is detected. For patients with locally advanced gastric cancer, sometimes doctors will directly operate on them, but sometimes they will recommend patients to have a dozen chemotherapy treatments before considering surgery. Why would you do this? The purpose of surgery is to remove the tumor completely, and the doctor will determine whether the tumor can be removed by examination before surgery. If the examination result tells the doctor that the tumor can be removed cleanly, the doctor will operate on the patient as soon as possible. If the tumor is large, or if it is not clearly demarcated from the surrounding organs, or if there are some lymph nodes around the tumor, these are the factors that may cause the tumor to not be removed cleanly, then the doctor may recommend chemotherapy first instead of surgery. Chemotherapy may reduce the size of the large lesion that could not be removed to a size that can be removed, and also reduce the size of the lymph nodes around the lesion, and also kill the tiny metastases that were not found during the examination. This turns an operation that might not be cleanly cut into one that can be completely removed, and fundamentally improves the patient’s outcome after surgery. This type of chemotherapy given before surgery is called “neoadjuvant chemotherapy”. Neoadjuvant chemotherapy not only helps to improve the resection rate of the surgery, but also has another important function, which is to conduct the in vivo drug sensitivity test in advance. Therefore, before playing chemotherapy, there are tumor lesions in the body, and according to the reaction of the lesions to the drugs, it can determine whether the drugs will be useful in the subsequent treatment, which can help to choose the chemotherapy plan to prevent tumor recurrence after surgery. 1.Does preoperative neoadjuvant chemotherapy really have benefits? Below, we introduce you several internationally known large-scale clinical studies that can tell you the benefits of neoadjuvant chemotherapy. The MAGIC study from the UK was the first to confirm the benefits of neoadjuvant chemotherapy for gastric cancer. This study randomized 503 patients into two groups, one group had surgery directly and the other group received three cycles of chemotherapy before and three cycles after surgery. The results showed that 69% of the patients who received chemotherapy achieved radical resection and a 5-year survival rate of 36%, while the radical resection rate for those who received direct surgery was 66% and the 5-year survival rate was only 23%. The FFCD 9703 study, initiated by French academics, also demonstrated the benefit of neoadjuvant chemotherapy. A total of 224 patients were divided into two groups, one with 2-3 cycles of preoperative chemotherapy with a fluorouracil + cisplatin regimen, and the other with direct surgery. The results showed that the radical resection rate in the chemotherapy group was nearly 10% higher than that in the surgery group, reaching 84%; the 5-year survival rate increased by nearly 15%, reaching 34%. 2. What are the main indications for neoadjuvant chemotherapy? The above data show that receiving neoadjuvant chemotherapy can bring obvious benefits to patients. Since 2008, the internationally adopted guidelines for gastric cancer treatment have recommended neoadjuvant chemotherapy for suitable patients. Some patients with locally progressive gastric cancer are difficult to be completely excised due to the depth of tumor invasion and lymph node metastasis. By taking neoadjuvant chemotherapy before surgery, these progressive gastric cancer lesions can be shrunken and the invasion of surrounding organs by the tumor and its affiliated lymph nodes can be reduced, so that radical resection can be achieved. These patients are the suitable patients for neoadjuvant chemotherapy. 3.What are the commonly used neoadjuvant chemotherapy regimens? The choice of neoadjuvant chemotherapy regimen should be decided according to the patient’s stage, age, high-risk factors, physical condition and concomitant diseases. Because the chance of radical surgical resection has to be strived for, the chemotherapy regimen should be moderately enhanced under the premise of ensuring safety, and single-drug chemotherapy is generally not chosen, but mostly a combination regimen of two types of drugs. For example: purple shirt + fluorouracil, purple shirt + platinum or platinum + fluorouracil. For patients with late stage, young and good physical condition, a combination of three types of drugs can be chosen, such as: purple shirt + platinum + fluorouracil. 4.What are the precautions for neoadjuvant chemotherapy? Firstly, the duration of chemotherapy should not be too long, usually 6~9 weeks. Secondly, the treatment effect should be evaluated in time so as not to miss the best time for surgery. Even if neoadjuvant chemotherapy is effective, it cannot keep on playing, and the good effect should be operated in time. Patients with ineffective results may find that the tumor progresses faster during the treatment and there is no chance of surgery at all, thus avoiding surgery that cannot be radical. Surgery is not immediately available after neoadjuvant chemotherapy. If the patient’s general condition allows, surgery is better to be performed about 3 weeks after chemotherapy is stopped. Why do I need chemotherapy after surgery? After surgery, the patient’s main concern is whether the surgery is clean or not. Will there be recurrence in the future? This is based on the surgical records and the post-operative pathology report. First of all, the surgical records will show whether the surgery is a standard D2 radical surgery. Secondly, from the pathology report, we can see whether the tumor is highly malignant, whether the stage is early or late, whether there is metastasis in the lymph nodes, whether the surgical margins are clean, whether the tumor has invaded the blood vessels or surrounding organs, etc. Based on these information, the doctor will determine whether the tumor has recurred. Based on the above information, doctors will judge the stage and prognosis of gastric cancer. By “prognosis”, it means whether the tumor has a great impact on life and whether the risk of recurrence is high. Generally speaking, after surgical lymph node dissection as described above, more than half of the patients will eventually have recurrence or metastasis. Two recent studies in Asia have shown that patients with gastric cancer have a survival benefit from adjuvant chemotherapy after D2 radical surgery, so we recommend adjuvant chemotherapy for patients with stage II and III gastric cancer after surgery. Adjuvant chemotherapy can help remove residual tumors and microscopic metastases that cannot be seen intraoperatively, can significantly reduce the risk of tumor recurrence and metastasis, and is an essential treatment for some patients. What is the evidence that adjuvant chemotherapy is beneficial to patients? In the treatment of gastric cancer, the importance of adjuvant chemotherapy was recognized earlier than that of neoadjuvant chemotherapy. So, is postoperative adjuvant chemotherapy effective or ineffective? Let’s take a look at a 2010 article published in JAMA, which conducted a meta-analysis of adjuvant therapy for 3838 gastric cancer patients in 17 studies worldwide. The results showed that receiving adjuvant chemotherapy after radical gastric cancer surgery significantly prolonged patients’ recurrence-free survival and overall survival time. The ACTS-GC study in Japan, CLASSIC in Korea, and the INT-0116 study in the United States are pivotal studies in the implementation of adjuvant chemotherapy after gastric cancer surgery, and they all strongly confirm that adjuvant chemotherapy for gastric cancer can significantly improve the survival rate of patients with intermediate and advanced stages (stages II and III), as described below. The ACTS-GC study is a clinical study initiated by Japanese scholars on the use of tegeo for adjuvant treatment of gastric cancer. The study randomized 1059 patients into two groups: the postoperative adjuvant tegeo group or the surgery-only group. As a result, at 1 year of postoperative tegeo, patients did not experience any serious adverse effects and had a 5-year survival rate of 71.7%, a 10% increase over the non-tegeo group; moreover, 65.4% of patients in the postoperative tegeo group did not experience recurrence at 5 years of follow-up, 12% higher than the other group. The CLASSIC study in Korea, which used capecitabine + oxaliplatin as a postoperative adjuvant treatment option for gastric cancer, is the only international multicenter clinical study that included Chinese patients (1,035 patients in total). Patients were randomized into two groups and received adjuvant chemotherapy for six months in the study. As a result, 74% of patients who received adjuvant chemotherapy were recurrence-free at three years postoperatively, compared with 59% of the surgery-only group. There was also a difference in overall survival between the two groups in a preliminary analysis, with an overall survival rate of 83% at 3 years in the adjuvant chemotherapy group compared to 78% in the surgery-only group. This study confirms that the capecitabine + oxaliplatin regimen of adjuvant chemotherapy has good recurrence prevention in patients with gastric cancer treated with surgery, with no patients experiencing serious adverse effects, and can be used as a standard regimen for the adjuvant treatment of gastric cancer. The INT-0116 study in the United States randomized 556 patients with gastric cancer into the postoperative concurrent chemoradiotherapy group and the surgery-only group. The specific treatment protocol for the chemoradiotherapy group was: 1 cycle of chemotherapy with fluorouracil + calcium folinic acid, followed by 5 weeks of local radiotherapy, and 2 cycles of chemotherapy continued after radiotherapy. The results showed that the survival of patients who did simultaneous chemoradiotherapy after surgery reached 3 years, which was 9 months more than that of patients who had surgery alone; the 3-year survival rate reached 51%, which was 10% higher than that of patients who had surgery only, which fully illustrated the benefits of postoperative adjuvant therapy for patients.