Early gastric cancer (EGC) is defined as tumor confined to the mucosa or submucosa, regardless of LNM in 1971 by Murakami[3]. Even though, other classifications, such as Kodama’s classification[12] and Paris’s classification[13] were also proposed to define EGC, the Murakami definition is the still the most widely adopted one in recent studies. In an era of precision medicine, the diagnosis, treatment and prognosis of EGC with or without LNM are completely different. Currently, EMR and ESD are first alternative choice for patients without LNM, while radical surgery is necessary for patients with LNM. Several reports have focused on the risk factors of LNM and indicated that the lymph node status was an important prognostic factor[6, 9, 14–16]. In addition, the indications for AC in T1N + M0 gastric cancer is T1N2-3bM0, according to the latest Japanese gastric cancer treatment guidelines 2018 (5th edition)[17]. Whether AC is really unnecessary for T1N1M0 gastric cancer remains to be decided, but few studies have focused on this topic. Therefore, we investigated the incidence and risk factors of LNM, and evaluate the survival of T1N + M0 gastric cancer using the SEER database.
In the present study, we found the LNM rate for patients with T1N + M0 gastric caner is 19.5%, which is comparable to previously reported 4%-24%[14, 18–20]. Our study also indicated that age, tumor size, invasion depth, type of differentiation and number of retrieved LNs were independent risk factors for LNM in EGC. Depth of invasion is the most important risk factors for LNM. Previous studies have reported the relationship of age and LNM. Higher risk for LNM was more indentified in young patients [21], and a lower risk in old patients [22]. However, other studies reported that LNM was not associated with age [23]. In the present study, old age (≥ 85) had a lower risk for LNM. Many previous reports have also confirmed that undifferentiated type is more aggressive[24], which was confirmed in our study.
In our study, the tumor size and depth of invasion are independent risk factors for LNM, which was consistent with previous studies [25]. Another important risk factor for LNM is the presence of lymphovascular invasion. However, among all these risk factors, depth of invasion might have the greatest impact.
In the present study, multivariate analyses showed age, sex, tumor size, invasion depth and LNM were related with OS and CSS. LNM has been identified as a significant predictor of OS by many studies. A study showed that the 5-year survival rate was 87.3% and 94.2% in EGC patients with LNM and without LNM, respectively. Roviello et al. reported that the 10-year OS in EGC patients was different for patients with different number of LNM. Patients with 1–3 LNMs had a lower risk of recurrence, while in cases with four or more LNMs, the risk of recurrence increased. Therefore, increased LNM was associated with decreased survival and higher recurrence rate.
If lymph node metastases are present, patients should receive AC after radical surgery according to the recommendations of the Chinese Society of Clinical Oncology and the European Society of Medical Oncology [17, 26]. However, AC are not recommended for patients with pT1N0M0 and pT1N1M0 according to the latest Japanese gastric cancer treatment guidelines 2018 (5th edition)[11]. Our study revealed that there were statistically significant differences in OS and CSS between pN0/N + or pN0-1/N2-3b categories (p༜0.001), but an overlap in survival curves was found between categories pN0-1/N2-3b. The proportion of patients in pN0/N + was better distributed and pN0/N + category showed improved prognostic performance in predicting OS and CSS. Moreover, multivariate analyses showed AC was associated with CSS. Therefore, pT1N1M0 may be appropriate candidate for AC, other studied have also showed these patients[27–29].
There are some limitations to our study. First, the retrospective study is based on SEER database, which represents only 28% of the U.S. population and lacks data on many medical details. Second, we just investigated the major risk factors in terms of LNM and prognosis, suggesting modification of the definition with tumor size, invasion depth and LNM. Further clinical studies are warranted to investigate more definitive parameters. The biological behavior and molecular mechanism of LNM in gastric cancer needs to be clarified. An updated definition, which combines macroscopic types, pathological morphology and molecular classification, may be useful to make appropriate treatment decisions and follow-up plans. Furthermore, a unified and standardized definition makes different studies comparable.