Prognostic analysis and application value of adjuvant chemotherapy after radical resection of stage Ⅰ gastric cancer (a nationwide and multicenter study of 6 366 cases)

Objective To investigate the prognostic factors of stage Ⅰ gastric cancer patients after radical resection and the application value of adjuvant chemotherapy.

Methods The multicenter real-world study was conducted. The clinicopathological data of 6 366 patients with stage Ⅰ gastric cancer who were admitted to 12 medical centers, including Fudan University Shanghai Cancer Center et al, from January 2000 to December 2024 were collected. There were 4 612 males and 1 754 females, aged 60 (range, 21-91) years. There were 3 936 cases in stage ⅠA and 2 430 cases in stage ⅠB. All patients underwent radical R₀ resection. Observation indicators: (1) clinicopathological characteristics; (2) analysis of postoperative prognostic factors; (3) relationship between postoperative adjuvant chemotherapy and prognosis. Comparison of count data between groups was conducted using the chi‑square test. Based on the clinically recognized factors affecting prognosis, the indicators with P<0.05 in the univariate analysis were incorporated into the multivariate analysis. The Cox proportional hazards regression model was used for univariate and multivariate analyses. The Kaplan⁃Meier method was used to calculate survival rates and plot survival curves. The Log‑rank test was used for survival analysis.

Results (1) Clinicopathological characteristics: of the 6 366 patients, there were 3 139 cases aged <60 years and 3 227 cases aged ≥60 years. There were 5 491 cases with stage T1 tumor including 2 735 cases of stage T1a and 2 756 cases of stage T1b, 875 cases with stage T2 tumor. There were 1 381 cases with tumor located in the cardia and fundus of stomach, 1 318 cases with tumor located in the gastric body and/or gastric angle, 3 667 cases with tumor located in the gastric antrum. There were 405 cases with well differentiated tumor, 2 859 cases with moderately differentiated tumor, 3 102 cases with poorly differentiated tumor. There were 9 cases receiving D₀ lymph node dissection, 1 476 cases receiving D₁ lymph node dissection, 2 795 cases receiving D₁₊ lymph node dissection, 2 086 cases receiving D₂ lymph node dissection. There were 528 cases with the number of lymph node dissected <16 and 5 838 cases with the number of lymph node dissected ≥16. There were 468 cases receiving proximal subtotal gastrectomy, 4 778 cases receiving distal subtotal gastrectomy, 1 102 cases receiving total gastrectomy, and 18 cases receiving middle segment gastrectomy. There were 5 355 cases with negative vascular invasion and 1 011 cases with positive vascular invasion. There were 5 376 cases with negative neural invasion and 990 cases with positive neural invasion. There were 5 833 cases with levels of carcinoembryonic antigen (CEA) <5 μg/L and 533 cases with levels of CEA ≥5 μg/L. There were 6 149 cases with levels of CA19-9 <37 U/mL and 217 cases with levels of CA19-9 ≥37 U/mL. There were 5 888 cases without post-operative adjuvant chemotherapy and 478 cases (including 181 cases in stage T1N0M0, 153 cases in stage T1N1M0, 144 cases in stage T2N0M0) with postoperative adjuvant chemotherapy. (2) Analysis of postoperative prognostic factors: results of multivariate analysis showed that male, age ≥60 years, stage T2 tumor, the number of lymph node dissected <16, surgical procedure as proximal subtotal gastrectomy and distal subtotal gastrectomy, positive vascular invasion, positive neural invasion, CEA ≥5 μg/L, CA19‑9 ≥37 U/mL were independent risk factors for 10‑year disease‑free survival time of patients with stage Ⅰ gastric cancer after radical resection hazard ratio (HR)=1.599, 2.507, 1.713, 0.576, 1.585, 0.724, 1.653, 0.657, 1.504, 1.628, 95% confidence interval (CI) as 1.194‒2.142, 1.973‒3.186, 1.268‒2.313, 0.438‒0.757, 1.107‒2.271, 0.545‒0.963, 1.232‒2.217, 0.470‒0.919, 1.094‒2.068, 1.040‒2.549, P<0.05. Male, age ≥60 years, stage T2 tumor, the number of lymph node dissected <16, surgical procedure as proximal subtotal gastrectomy and distal subtotal gastrectomy, positive vascular invasion, CA19‑9 ≥37 U/mL were independent risk factors for 10‑year overall survival time of patients with stage Ⅰ gastric cancer after radical resection (HR=1.483, 4.010, 1.366, 0.761, 1.630, 1.316, 1.376, 1.560, 95%CI as 1.186‒1.853, 3.255‒4.940, 1.051‒1.776, 0.597‒0.970, 1.154‒2.302, 1.018‒1.702, 1.086‒1.744, 1.069‒2.278, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for the 10‑year overall survival time of patients with stage Ⅰ gastric cancer after radical resection (HR=0.559, 95%CI as 0.358‒0.874, P<0.05). (3) Relationship between postoperative adjuvant chemotherapy and prognosis. The 10‑year disease‑free survival rates of patients with and without postoperative adjuvant chemotherapy were 91.0% and 90.9%, the 10‑year overall survival rates were 90.2% and 86.3%, respectively, showing no significant difference in 10‑year disease‑free survival rate (χ²=0.015, P>0.05), but a significant difference in 10‑year overall survival rate between them (χ²=6.691, P<0.05). The 10‑year disease‑free survival rates of patients in stage T1N0M0, stage T1N1M0, stage T2N0M0 who received postoperative adjuvant chemotherapy were 87.3%, 92.8%, 95.6%, the 10‑year overall survival rates were 88.8%, 88.7%, 95.0%, respectively, showing no significant difference in the above indicators among them (P>0.05). The 10‑year disease-free survival rates of patients in stage T1N0M0, stage T1N1M0, stage T2N0M0 who did not receive postoperative adjuvant chemotherapy were 92.4%, 91.1%, 82.3%, the 10‑year overall survival rates were 87.2%, 89.0%, 78.5%, respectively, showing significant differences in the above indicators among them (P<0.05).

Conclusions Male, age≥60 years, stage T2 tumor, the number of lymph node dissected <16, positive vascular invasion, and CA19‑9 ≥37 U/mL are independent risk factors affecting the postoperative prognosis of stage Ⅰ gastric cancer, and postoperative adjuvant chemo-therapy is an independent protective factor for the 10-year overall survival time. Compared with patients in stage T1N1M0, patients in stage T2N0M0 have a higher risk of postoperative recurrence and survival, and postoperative adjuvant chemotherapy can better improve their survival benefits.