Patient characteristics
A total of 857 patients diagnosed with g-NENs without distant metastasis from SEER database were analyzed in this study. The median age at diagnosis was 60 years (range: 17-99 years). There were 350 (40.8%) males and 507 (59.2%) females (female-male ratio of 1.45). The distribution of g-NENs from SEER dataset was gastric body (29.4%, 252/857), cardia and gastric fundus (18.1%, 155/857), antrum and pylorus (10.6%, 91/857), and unspecified parts of the stomach (23.3%, 200/857). In terms of tumor size, 490/587 patients (57.2%) were less than 1cm, 203/587 patients (23.7%) were larger than 2cm and 164/587 patients (19.1%) were between 1 to 2 cm. Most of the patients were well-differentiated (88.2%). Lymph node metastasis were found in 138 (16.1%) of all patients.
A total of 72 patients from Wuhan Union Hospital and the First Affiliated Hospital of Shihezi University from 2009 to 2019 were collected and assigned as the clinical dataset (clinical characteristics were presented in Table 1). The median age at the diagnosis was 59 years (range: 32-86). There were 23 (31.9%) females and 49 males (68.1%). Cardia and gastric fundus (40.3%, 29/72) was the most common tumor site, followed by gastric body (29.2%, 21/72), and antrum and pylorus (15/72, 20.8%). In terms of tumor size, 16/72 patients (22.2%) were less than 1cm, 45/72 patients (62.5%) were larger than 2 cm and 11/72 patients (15.3%) were between 1 to 2 cm. Lymph node metastasis occurred in 32 (44.4%) patients.
Endoscopic resection vs. surgical resection for g-NENs without distant metastasis
Tumor size
A total of 743 (86.7%) of patients in the SEER dataset and 66 (91.7%) of patients in the clinical dataset received resection treatment. Overall, K-M analysis showed that patients who underwent resection had a better prognosis than those who did not, both in the SEER dataset (p=0.0019, Figure 1A) and in the clinical dataset (p=0.0004, Figure 1E). Next, we compared the prognosis between resection group and unresected group based on tumor size. For tumors larger than 2 cm, the resection group had a better prognosis than unresected group both in the SEER dataset (p=0.0002, Figure 1B) and in the clinical dataset (p=0.0011, Figure 1F). However, for tumors smaller than 1 cm and those between 1 and 2 cm in size, there was no significant difference in survival between resection group and unresected group (p>0.05, Figure 1C, D and G).
Moreover, we further analyzed and compared the prognosis of patients with tumors larger than 2 cm with different resection methods. In the SEER dataset, 178 patients with tumors larger than 2 cm underwent resection, of which 31/178 (17.4%) underwent endoscopic resection and 147/178 (82.6%) underwent surgical resection. For tumors larger than 2 cm, K-M analysis showed that there was no significant difference in survival between endoscopic resection group and surgical resection group (p=0.0588, Figure 2A). For tumors larger than 2cm that underwent resection, the median tumor size was 2.5 cm in endoscopic resection group and 4.0 cm in surgical resection group (p<0.001, Table 2). For tumors smaller than 1cm or those between 1 and 2 cm in size, there was also no significant difference in survival between endoscopic resection group and surgical resection group (p>0.05, Figure 2B and C).
Depth of tumor invasion
In this study, the SEER dataset was analyzed to investigate the relationship between the depth of tumor invasion and the outcome of different resection methods. In the resected group, in-situ tumors accounted for 5.1% (38/743), T1 50.9% (378/743), T2 28.1% (209/743), T3 10.9% (81/743) and T4 5.0% (37/743). For tumors larger than 2cm confined to in-situ and T1, the prognosis was similar between the endoscopic resection group and the surgical resection group (p=0.2457, Figure 3A). For tumors smaller than 1 cm or between 1 and 2 cm confined to in-situ and T1, there was also no significant difference between endoscopic resection group and surgical resection group (p>0.05, Figure 3B and C). Therefore, we conclude that endoscopic resection and surgical resection are feasible for g-NENs limited to in-situ and T1, whether smaller than 1cm, between 1 and 2 cm or larger than 2 cm.
Lymph node metastasis
The relationship between lymph node metastasis and the prognosis of different resection methods was also explored. In g-NENs patients without lymph node metastasis (618/743, 83.2%), there was no difference in prognosis between the endoscopic resection group and the surgical resection group, whether the tumor was smaller than 1 cm, between 1 and 2 cm or larger than 2 cm. (p>0.05, Figure 4A-C). More importantly, in patients with lymph node metastasis (125/743, 16.8%), no difference in prognosis was found between the endoscopic resection group and the surgical resection group, whether smaller than 1 cm, between 1 and 2 cm or larger than 2 cm (p>0.05, Figure 4D-F).
Differentiation
Furthermore, the prognosis difference between different resection methods in well-differentiated g-NENs was compared. The results showed that the prognosis of the endoscopic resection group was similar to that of the surgical resection group, whether the tumor was smaller than 1 cm, larger than 2 cm, or between 1 and 2 cm in size (p>0.05, Figure 5A-C). Due to the limited number of patients with poorly-differentiated morphology undergoing endoscopic resection, we were unable to compare the difference in survival between the endoscopic resection group and surgical resection group based on tumor size.
Prognostic analysis
To further investigate the prognostic factors related to the prognosis of g-NENs without distant metastasis, we conducted univariate analysis, including age, sex, race, differentiation, tumor site, tumor size, TNM stage, T stage, N stage, whether or not resection treatment was given and resection methods. Results of univariate and multivariate Cox regression analysis for survival were summarized in Table 3. The Cox regression analysis showed that age≥55 (p=0.002), poorly-differentiation (p=0.001), tumor larger than 2cm (p=0.020) and not receiving resection treatment (p=0.000114) were negative prognostic factors for survival of g-NENs patients without distant metastasis.