Survival outcomes in early gastric cancer: evidence from SEER-based population studies

Gastric cancer remains a leading cause of cancer-related mortality worldwide, despite declining incidence in many regions. Early gastric cancer (EGC) represents a subset of gastric cancer confined to the mucosa or submucosa and is associated with excellent prognosis when appropriately treated. Five-year survival rates exceeding 90% have been reported in surgical and endoscopic series, particularly from East Asia (1,2). Population-level outcomes in Western countries are less well characterized, and substantial heterogeneity in survival persists even among patients with early-stage disease. The prognosis within EGC is heterogeneous and influenced by some factors: tumor-, patient-, and treatment-related factors. Large population-based databases, particularly the Surveillance, Epidemiology, and End Results (SEER) program, have enabled detailed evaluation of survival determinants in cancers across diverse patient populations. This review synthesizes findings from representative SEER-based studies that evaluate survival in EGC, with particular attention to tumor location (cardia vs. non-cardia), lymph node status, treatment modality, and methodological advances in population-based research.

Methodological considerations, including competing risk analysis and propensity score matching (PSM), are discussed. Collectively, SEER-based evidence supports the concept that EGC is a biologically heterogeneous diseases and that tumor location and nodal status remain key prognostic determinants even at an early stage (3-5). SEER-based studies commonly evaluate overall survival (OS, capturing all-cause mortality), disease specific survival (DSS, death attributable to gastric cancer). DSS is particularly valuable in EGC, where non-cancer-related mortality may be substantial, especially in elderly populations. Early SEER studies primarily relied on Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression (3). More recent analyses have incorporated PSM to reduce baseline imbalance and developed nomograms for individualized risk prediction (6,7). These methodological advances have improved the robustness and clinical relevance of SEER-based EGC research.

To evaluate prognostic factors within EGC is clinically important for several reasons. First, risk stratification informs treatment selection, particularly the appropriateness of endoscopic resection versus gastrectomy with lymphadenectomy. Second, identification of high-risk subgroups may guide surveillance strategies and adjuvant therapy considerations. Third, prognostic modeling in EGC provides insight into tumor biology and disease progression. Treatment modality is well associated with survival outcomes. Gastrectomy remains the standard treatment for most EGC patients in SEER cohorts (8). Surgical resection consistently conducts favorable long-term survival, particularly when combined with adequate lymph node evaluation. Direct identification of endoscopic resection in SEER is limited. However, indirect comparisons using treatment codes and PSM have suggested that selected low-risk T1a patients experience comparable DSS with non-surgical management compared with surgery (9). These findings align with Eastern data and support the expanding role of endoscopic therapy in carefully selected patients. SEER-based studies generally do not demonstrate a clear survival benefit for adjuvant radiotherapy or chemotherapy in surgically treated EGC, particularly in node-negative disease (10). These observations are consistent with current guideline recommendations and reflect the favorable natural history of early-stage tumors (11-13).

In SEER analyses, EGC is usually defined by pathologic stage as T1 gastric cancer (T1a or T1b) per American Joint Committee on Cancer (AJCC) staging. Japanese guidelines (13), which define EGC irrespective of nodal status, some SEER studies further restrict EGC to stage I disease or T1N0 tumors due to concerns regarding heterogeneity. The differences within guidelines should be considered with caution (14). SEER data reveal that EGC accounts for a minority of gastric cancer cases in the United States, reflecting the lack of population-wide gastric cancer screening programs. Patients with EGC in SEER cohorts tend to be older and more frequently male, with a higher proportion of cardia tumors compared with the East Asian series. These epidemiologic differences underscore the importance of population-based studies in understanding Western EGC outcomes.

One of the most consistent findings across SEER-based studies is the prognostic importance of lymph node involvement, even in early-stage disease (7,15,16). Analyses of T1 gastric cancer cohorts demonstrate that patients with nodal metastasis experience significantly worse OS and DSS compared with node-negative patients. Several studies have further shown that the number of lymph nodes examined is independently associated with survival. Adequate nodal evaluation likely reflects both surgical quality and stage migration effects. These findings reinforce the oncologic importance of lymphadenectomy in EGC patients undergoing gastrectomy and highlight limitations in staging accuracy for patients treated non-surgically. Depth of invasion within the T1 category (T1a vs. T1b) has been repeatedly identified as a prognostic factor in SEER analyses (17). Submucosal invasion (T1b) is associated with higher rates of nodal metastasis and worse survival outcomes compared with intramucosal disease. Histologic grade is another consistent determinant of prognosis (18). Poorly differentiated and undifferentiated tumors are associated with inferior DSS, even after adjustment for stage and treatment. Tumor size, while variably reported, has also been linked to survival, with larger tumors portending worse outcomes (19,20). Patient-related factors, particularly age, exert a strong influence on OS. SEER studies employing competing risk models demonstrate that non-cancer-related mortality accounts for a substantial proportion of deaths among elderly EGC patients, emphasizing the need to interpret OS cautiously in this population.

Anatomical tumor location has emerged as an important prognostic variable in gastric cancer. Several SEER-based studies have specifically examined survival differences between gastric cardia cancer (GCC) and gastric non-cardia cancer (GNCC). In the recent issue of the Journal of Gastrointestinal Oncology, Ma et al. (21) reported a SEER database analysis comparing the clinicopathological feature and prognosis between early GCC (EGCC) and early GNCC (EGNCC). The inclusion criteria of the study are surgically resected EGC infiltration depth limited to T1a or T1b, and exclusion criteria are patients who received additional therapy such as radiotherapy or chemotherapy. Then, they demonstrate that the EGCC group exhibit a notably lower median survival time than the EGNCC group. Their finding suggests that the survival outcome of EGCC depends on the depth of tumor infiltration. When the tumor is confined to the mucosal layer, no significant survival differences between EGCC and EGNCC patients are observed. However, the landscape shifts when tumors penetrate the submucosal layer. The results reveal a significant disparity in survival rates between patients with EGCC and EGNCC when the tumor is limited to the submucosal layer. From the case-control analyses, GCC is associated with younger patient age, male predominance, higher comorbidity burden, and more advanced local features, even within T1 disease. Unadjusted analyses typically demonstrate worse DSS and OS for GCC compared with GNCC (22). After multivariable adjustment, the survival disadvantage of cardia tumors is often attenuated but may persist, particularly for DSS. OS differences are less consistent, suggesting that non-cancer-related mortality contributes substantially to observed disparities. Importantly, PSM-based analyses indicate that tumor location may remain an independent DSS in surgically treated EGC, supporting the concept that cardia and non-cardia tumors represent biologically distinct entities even at an early stage.

Traditional survival analyses may overestimate cancer-specific mortality in EGC by failing to account for competing risks. Non-cancer-related death represents a major competing event, especially in older patients. Tumor-related factors primarily influence DSS, whereas patient-related factors drive OS. These findings have important implications for clinical decision-making, particularly in elderly or frail patients where aggressive treatment may not translate into meaningful survival benefit. Several SEER-based studies have developed prognostic nomograms for EGC incorporating variables such as age, tumor size, grade, depth of invasion, lymph node status, and tumor location (7,17). These models demonstrate good discriminatory ability and calibration, highlighting the feasibility of individualized risk prediction using population-based data. Incorporation of tumor location into these models further improves prognostic accuracy, reinforcing its clinical relevance.

Despite their strengths, SEER-based studies have inherent limitations in retrospective design. Misclassification of gastroesophageal junction and cardia tumors are potential. Clinically important data including recurrence and molecular types are absent. These limitations necessitate cautious interpretation and underscore the need for complementary prospective and translational studies. The collective SEER-based evidence demonstrates that EGC is not a uniform disease entity. Prognosis is influenced by lymph node status, tumor depth, histologic features, patient age, and tumor location. Recognition of these factors is essential for optimizing treatment selection and follow-up strategies. Future research should focus on several issues. Integrating population-based data with molecular profiling, refining definitions of cardia and gastroesophageal junction tumors, validating SEER-based findings in international cohorts, and developing location-specific and risk-adapted management strategies are investigated.

SEER-based population studies have substantially advanced understanding of survival outcomes in EGC. Even at an early stage, prognosis is heterogeneous and influenced by multiple clinicopathologic factors, including anatomical tumor location. Evidence suggests that EGCC and EGNCC differ in survival patterns, reflecting underlying biological and epidemiologic differences. While SEER analyses cannot replace prospective trials, they provide critical population-level insights that inform clinical practice and future research.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Gastrointestinal Oncology. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0114/coif). The authors have no conflicts of interest to declare.

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