Prognostic Comparison Between Early Gastric Signet Ring Cell Carcinoma and Non-Signet Ring Cell Carcinoma: A Large-Sample Matched Study with External Single-Center Validation

Abstract Background: While gastric signet ring cell carcinoma (SRCC) is traditionally considered aggressive, emerging evidence suggests a "prognostic paradox" wherein early-stage SRCC may exhibit favorable outcomes. The comparative prognosis between early gastric SRCC and non-SRCC (NSRCC) remains controversial and requires large-scale validation. Methods: This retrospective cohort study analyzed 6,758 stage I gastric cancer patients from the SEER database (2010–2019; SRCC: n = 645, NSRCC: n = 6,112). 1:1 propensity score matching (PSM) balanced baseline characteristics (age, gender, Grade classification, pathological T and N stages, number of regional lymph nodes removed, postoperative chemotherapy/radiotherapy status, tumor size, number of harvested lymph nodes, and marital status). Overall survival (OS) and cancer-specific survival (CSS) were compared using Kaplan-Meier/log-rank tests. Multivariable Cox regression identified independent prognostic factors. An external cohort (n = 52) was included for validation. Results: Before PSM, SRCC showed better OS than NSRCC (P = 0.0035) but comparable CSS (P= 0.26). After PSM, no significant differences existed in OS (log-rank P= 0.71) or CSS (P = 0.50). External validation confirmed no survival difference (P > 0.05). Multivariable analysis identified independent risk factors: age ≥ 65 years (HR 2.360, 95%CI 2.038 - 2.734, P< 0.001), male gender (HR 1.567, 95%CI 1.365 - 1.798, P < 0.001), Grade II (HR 1.569, 95%CI 1.205 - 2.043, P = 0.001), Grade III (HR 2.193, 95%CI 1.689 - 2.847, P < 0.001), Grade IV (HR 3.047, 95%CI 1.772 - 5.239, P < 0.001), AJCC_NN1 (HR 1.382, 95%CI 1.107 - 1.724, P= 0.004), no regional lymph node dissection (HR 2.107, 95%CI 1.508 - 2.945, P< 0.001), postoperative radiotherapy (HR 2.062, 95%CI 1.691 - 2.515, P< 0.001), tumor size > 10 mm (HR 4.261, 95%CI 3.451 - 5.262, P< 0.001), and marital status (HR 1.385, 95%CI 1.219 - 1.572, P < 0.001) . The number of retrieved lymph nodes ≥ 12 LNS was protective (HR 0.747, 95%CI 0.618 - 0.903, P = 0.003). Conclusion: Early-stage SRCC and NSRCC have comparable long-term survival after confounding adjustment. Key prognostic factors include age ≥65, male sex, poor differentiation, large tumor size, lymph node metastasis, inadequate lymphadenectomy, and unmarried status. Adequate lymph node dissection (≥12 nodes) significantly improves survival, underscoring the critical role of standardized surgical quality in early gastric cancer management.