Early gastric cancer (EGC) is defined as a tumor confined to the mucosa or submucosa, regardless of lymph node metastasis. This concept was first proposed by the Japanese Gastric Cancer Research Association in 1962 and has been used up until now (Katai and Sano, 2005). For EGC patients who do not have lymph node metastasis and meet the indications for endoscopic mucosal resection and endoscopic submucosal dissection, minimally invasive endoscopic treatment can completely remove the lesions (Lian et al., 2012; El-Sedfy et al., 2014; Ono et al., 2016; Suzuki et al., 2016; Tanoue et al., 2019). Although endoscopic resection is the preferred option for EGC patients in accordance with indications, the impossibility of regional lymph node clearance is a serious limitation. Approximately 8.9–15.8% of EGC cases will have regional lymph node metastasis, which may lead to tumor recurrence and the need for invasive radical gastrectomy (Roviello et al., 2006; Pessorrusso et al., 2018). Radical surgical treatment can achieve sufficient tumor clearance and lymph node dissection range and its recurrence rate is low, with a 5-year survival rate of >90% (Zeng et al., 2012). The risk of postoperative recurrence in EGC with lymph node metastasis is high, and it is still unclear whether postoperative adjuvant chemotherapy (ACT) can benefit patients with a high risk of such recurrence and poor prognosis.

Clinical research on gastric cancer ACT is mainly focused on advanced gastric cancer, while research on EGC ACT alone is less prevalent (Cai et al., 2018; Yoshida et al., 2019). Although the NCCN guidelines recommend that patients at T stage accompanied by N + should receive ACT after surgery (Ajani et al., 2013), the Japanese guidelines for the treatment of gastric cancer recommend postoperative observation of EGC patients (Japanese gastric cancer, 2017). There are few clinical trials on ACT indications, which makes it more difficult to make postoperative treatment decisions for EGC patients.

A nomogram is a scoring tool used to quantify the likelihood of clinical events in combination with a variety of factors, which has been widely accepted internationally in recent years. Studies have shown that a nomogram is more accurate in assessing clinical events than a traditional prediction model (Balachandran et al., 2015; Hoban et al., 2018). However, a nomogram for predicting overall survival (OS) for EGC is still not established. Therefore, this study aimed to establish a nomogram that can evaluate the prognosis EGC patients based on a variety of clinicopathological factors in the Surveillance, Epidemiology, and End Results (SEER) database and to solve the problem of patient selection for EGC ACT.

Gastric cancer can be divided into EGC and advanced gastric cancer according to the degree of disease progression. EGC has a good prognosis, and its 5-year survival rate is significantly higher than that of advanced gastric cancer. Therefore, it is particularly important to improve EGC detection rate and provide effective treatment plans to reduce its mortality and improve the 5-year survival rate. Up until now, endoscopic resection and modified radical surgery have been accepted by many scholars. However, 2.7% of patients still experienced recurrence, and the recurrence rate in patients with lymph node metastasis reached ∼10% (Lai et al., 2009). Lymph node metastasis, invasion depth, and differentiation degree are all risk factors for EGC recurrence, while lymph node metastasis is the most important one. However, whether ACT can improve the prognosis of EGC patients with a high recurrence risk and poor prognosis, such as pT1N1, remains undecided (Shin et al., 2017; Kim et al., 2018). The economic burden and side effects of ACT are also factors that need to be considered. To achieve the maximum clinical benefit, patients with different outcomes require different treatment strategies. Therefore, the present study established a nomogram based on the SEER database and analyzed whether patients with different risk factors can benefit from ACT, hoping to provide a more accurate decision basis for the treatment of EGC patients.

Previous studies have shown that the factors affecting the prognosis of EGC include low degree of differentiation, lymph node metastasis, and advanced age (Cheong et al., 2006; Du et al., 2012). The risk factors were re-evaluated in the present study. Age, race, marital status, primary site, histology, grade, surgical extent, and rN were determined to be independent prognostic factors. Elderly patients have more complicated diseases, decreased organ function, greater surgical risk, more postoperative complications, and poor long-term prognosis. The present study found that prognosis for individuals aged ≥65 years was poor (HR = 2.122; 95% CI: 1.729–2.605; p < 0.001), which is consistent with previous research results (Jang et al., 2013). It was also found that the prognosis of cardiac EGC was poor compared to other sites. Patients with proximal gastric cancer had a high proportion of individuals aged ≥65 years, the tumor size was large, while the lymph node metastasis rate was high, all of which explain the poor prognosis (Petrelli et al., 2017; Yu et al., 2018). The Asian/Pacific Islander (API) prognosis was better than that of whites (HR = 0.735; 95% CI: 0.607–0.891; p = 0.002), which may be related to its lower incidence (Islami et al., 2019). Kunz et al. (Kunz et al., 2012) have also found that API had a better prognosis than that of whites (HR = 0.766; 95% CI: 0.727–0.806; p < 0.05), which was consistent with the present study. In cancer, unmarried status was also associated with poor prognosis, which may be related to the psychological and economic factors, as well as unwillingness to receive treatment (Li and Hu, 2019).

In the past, it was generally believed that signet ring cell carcinoma has a high degree of malignancy and a poor prognosis. However, continuous study of this type of disease found that signet ring cell carcinoma prognosis at different stages is significantly different. The advanced signet ring cell carcinoma prognosis is very poor, while early-stage prognosis is better than that of adenocarcinoma (Chon et al., 2017). Kim et al. (2017) believed that gastric signet ring cell carcinoma of pT1a is not associated with lymph node metastasis regardless of tumor size, while adenocarcinoma is an independent risk factor for lymph node metastasis. The present study also showed that signet ring cell carcinoma has a better prognosis than adenocarcinoma (HR = 0.655; 95% CI: 0.508–0.844; p = 0.001).

Undifferentiated EGC is highly malignant, aggressive, and prone to early metastasis. Feng et al. (Feng et al., 2016) have studied 976 EGC patients and found that the incidence of lymph node metastasis was 6.6% in differentiated and 20.5% in undifferentiated ECG patients. The present study also found that the prognosis of undifferentiated adenocarcinoma is worse than that of differentiated adenocarcinoma (HR = 1.323; 95% CI: 1.113–1.573; p = 0.002). In addition, patients with undifferentiated adenocarcinoma could not receive minimally invasive endoscopic treatment. The present study also found that expanded surgery results in poor prognosis (HR = 1.543; 95% CI: 1.242–1.916; p < 0.001). The larger the surgical extent, the greater the probability of patients undergoing unnecessary or excessive lymph node dissection and the greater the postoperative trauma and complications, which are also the reasons for poor prognosis in such patients.

Lymph node metastasis is considered to be one of the important factors affecting the prognosis of patients with gastric cancer. Accurate and reasonable lymph node staging is of great significance for determining the course of disease, evaluating the prognosis, and formulating a reasonable treatment plan. While inheriting and developing the classical lymph node staging system for gastric cancer, major research centers are also working on new methods of lymph node staging related to the prognosis of gastric cancer, such as using rN, which is defined as the number of positive lymph nodes/total number of lymph nodes dissected. A prognostic analysis of 1,075 gastric cancer patients performed by Zhou et al. (2013) indicated that no matter how many lymph nodes were examined, rN staging provided a better prediction of patient prognosis than N staging and suggested that rN staging should replace N staging to predict lymph node status. A study of 9,357 gastric cancer patients from the SEER database showed that in the vast majority of Western gastric cancer patients undergoing localized lymph node dissection, rN can effectively predict patient prognosis and can be divided into four stages: rN0 (0), rN1 (∼1–20%), rN2 (∼21–50%), and rN3 (∼51–100%) (Kutlu et al., 2015). This staging method was also used in the present study and found that the prognosis of rN1, rN2, and rN3 patients was worse than that of rN0 patients (HR = 2.126; 95% CI: 1.715–2.635; p < 0.001, HR = 2.931; 95% CI: 2.226–3.858; p < 0.001, HR = 4.693; 95% CI: 3.331–6.613; p < 0.001, respectively). Cheong et al. (Cheong et al., 2006) have found that the 5-year survival rates in EGC patients were 94.0 and 72.6% for rN < 0.07 and rN > 0.07, respectively. This is consistent with the present results. At the same time, the nomogram based on these prognostic factors has good discrimination and repeatability characteristics. The nomogram C-index was 0.730 (95% CI: 0.677–0.783), which was significantly higher than the C-index for the 8th AJCC TNM staging of 0.534 (95% CI: 0.507–0.561), indicating that the present study nomogram had a stronger predictive ability for EGC prognosis than the traditional TNM staging system. The DCA curve suggested better estimation for decision making.

It is controversial whether ACT should be performed after surgery in EGC. The present study showed that ACT did not have survival benefits in the whole patient before or after PSM analysis. This is mainly due to the fact that ACT is often used in clinical patients with poor prognostic factors, who also account for a small proportion of the total cohort. In this study, X-tile software was used to select two cutoff values (100 and 186) according to the patient’s risk score and divided the patients into low-, moderate-, and high-risk groups. In all of the patient group, including non-ACT and ACT groups, there was a significant difference in patient survival among low-, moderate-, and high-risk groups, indicating that risk stratification was reasonable and effective. While investigating who can really benefit from ACT, the 5-year survival rate in low-risk patients receiving ACT was found to be lower than that in patients who did not receive ACT (83.5 vs. 84.4%, p > 0.05). Therefore, ACT is not recommended for low-risk patients because its harmful effects outweigh its benefits. The 5-year survival rate in moderate-risk patients who received ACT was higher than that in patients who did not (66.9 vs. 59.6%, p < 0.01), indicating that moderate-risk patients can benefit from ACT. Patients in the high-risk group receiving ACT had a higher 5-year survival rate than those who did not receive ACT (44.3 vs.19.0%, p < 0.001), indicating that high-risk patients can benefit from ACT. The external validation also verified that high-risk patients can benefit from ACT. Therefore, ACT is suggested for moderate- and high-risk EGC patients after the operation.

The present research has several limitations. 1) This was a retrospective study, such as signet ring cell carcinoma or undifferentiated EGC has repeated parts, which may lead to bias. 2) The SEER database fails to provide specific ACT regimens, efficacy, and course of treatment, which affect the assessment of ACT efficacy. 3) Some EGC patients were not included in this study due to lack of data, leading to selection bias. 4) Progression-free survival was not evaluated in the present study, and other confounding factors may be involved in the overall survival, resulting in poor tumor survival assessment. 5) A nomogram that is applicable for the SEER and our center’s databases, as well as more studies from other centers, are needed. At present, no survival and prognosis model for EGC incorporates the above clinicopathological factors. Most importantly, this model was used to carry out risk stratification analysis for patients, which is of great significance for guiding clinical ACT. Since there has been no conclusion on whether EGC patients should receive ACT after surgery and the rate of EGC patients receiving ACT is generally low, it is difficult to carry out large RCT studies, which also highlights the importance of the present study.

The nomogram in the present study can effectively predict EGC patient prognosis. Patients at moderate and high risk are recommended to receive ACT based on risk stratification analysis, while patients at low risk are not.