The incidence of EGC in western countries is much lower than in Asian countries. In Asian countries, the number of new cases of early gastric cancer accounts for approximately 50% of the total[17]. Asian countries, especially Japan, have conducted a large number of studies on the treatment of EGC and formulated relevant treatment standards. Endoscopic mucosectomy and endoscopic submucosal dissection have been widely used in the treatment of EGC and have been established as the standard methods of endoscopic resection of early upper gastrointestinal tumors in Japan[18]. Compared with Asian countries, the progress of endoscopic treatment technology in western countries is relatively slow, and the treatment of EGC is still based on radical surgical resection[19, 20]. Therefore, it is not clear whether EGC is suitable for endoscopic therapy in western populations, especially for patients who are candidates for endoscopic therapy. In addition, at present, the sensitivity and specificity of endoscopic ultrasonography and CT and other imaging examinations for the determination of EGC lymph node metastasis are not ideal[21, 22], and the preoperative prediction of lymph node metastasis is not reliable. Analyzing the relationship between the clinicopathological features of EGC patients and lymph node metastasis can be used as a supplementary means for the preoperative diagnosis of lymph node metastasis to more clearly define the treatment of EGC patients.
Lymph node metastasis is a major factor in the endoscopic treatment and prognosis of EGC patients[23, 24]. In this study, we found that the lymph node metastasis rate of stage T1 gastric cancer after surgical resection was 14.5% (333/2294). Studies from Asia have shown that the rate of lymph node metastasis in EGC is 10-25.3%[12, 25], which is consistent with our findings. Patients less than 50 years old are more likely to develop LNM than patients in other age groups. When the subgroups were stratified by tumor location, the incidence of gastric pyloric tumor LNM was the highest. This phenomenon may be due to the multiple sets of lymph nodes near the pylorus. The risk factors for lymph node metastasis in western countries are similar to those in Asian countries. However, the ethnicities of Asian populations are relatively homogeneous. In western populations, the lymph node metastasis rate and survival prognosis are different between different races. The potential risk of lymph node metastasis in white EGC patients is lower than those of blacks or American Indians and Asia-Pacific Islanders.
The treatment of early gastric cancer includes endoscopic resection and radical surgery. For endoscopic resection treatment, the American Gastroenterology Association (AGA) updated the clinical practice of endoscopic submucosal dissection in 2019, indicating that absolute indications for EGC endoscopic treatment include moderate and well-differentiated, ulcer-free mucosal lesions with a size <2 cm; the expanded indications were moderate and well-differentiated superficial cancers, >2 cm, lesions <3 cm that are ulcerative or containing early submucosal infiltration, and poorly differentiated <2 cm superficial cancers[26]. From our results, it can be seen that when the tumor is a poorly differentiated or undifferentiated submucosal tumor with a size >2 cm, the rate of lymph node metastasis will increase 2-4 times. Therefore, the expanded indications of endoscopic treatment in western countries should be employed with caution.In this study, we developed and validated a predictive model for evaluating LNM in EGC patients.With the help of the prediction model, we can accurately determine the high-risk patients with EGC at LNM and choose the best surgical treatment.
This study analyzed the survival prognosis of 2294 patients. The results showed that EGC patients with lymph node metastasis had the worst prognosis, which may be related to the likelihood of tumor recurrence caused by lymph node metastasis. At the same time, advanced age, male size, large tumor size and stage T1b result in the poor prognosis of EGC patients. It is worth noting that race also affects the survival prognosis of EGC patients. Our results show that American Indians and Asian Pacific Islanders have a better prognosis than black and white patients, with black patients having the worst prognosis. The etiology of the difference in lymph node metastasis and survival outcome of EGC among different races is still unclear. The inherent molecular and biological differences between different ethnic groups may be the causes of the differences in survival among heterogeneous Western populations.
Studies in Asian countries have shown that the 5-year survival rate of EGC patients after effective treatment can reach more than 90%[27-29]. In this study, the Kaplan-Meier method was used to analyze the survival rate of EGC patients. The results showed that the 5-year tumor-specific survival rate of EGC patients without lymph node metastasis was 88.7%, and the 5-year tumor-specific survival rate of EGC patients with T1a was 91.4%. This is similar to the 5-year survival rate of the Asian population. In other words, EGC patients without lymph node metastasis and T1a western populations can benefit from endoscopic treatment.We have also developed and validated a prognostic model for cancer-specific survival of patients with EGC. For patients with a high risk of poor prognosis, surgical resection and lymph node dissection alone are not enough, and further adjuvant treatment may be needed.
This study has some limitations and advantages. The SEER database was used in this study, which does not capture tumor ulcers, lymphatic infiltration, and other indicators that have been shown to be risk factors for lymph node metastasis in EGC patients in Asian countries and should be taken into account when deciding treatment for EGC patients[30, 31]. Moreover, the SEER database covers only 28% of the U.S. population, with the possibility of sampling error. However, the SEER database is one of the largest registries allowing comparative analysis of EGC, providing a large sample size to assess risk factors for lymph node metastasis and survival outcomes in EGC patients by analyzing commonly used but often overlooked clinicopathological features.Finally, patients receiving adjuvant chemoradiotherapy were not included in this study, so an analysis of this specific population may be required.
In summary, tumor size, tumor grade and tumor infiltration depth are risk factors for lymph node metastasis of EGC.Endoscopic therapy for differentiated intramucosal tumors is an alternative therapy.For patients with prognostic risk factors, surgical treatment and lymph node dissection alone are not enough, and adjuvant therapy may be needed to improve survival rate.In this study, we established a reliable prediction model for lymph node metastasis of early gastric cancer and a prognostic model for early gastric cancer, providing a good basis for clinical treatment decision making.