Abstract
BACKGROUND: Advanced gastric and colorectal signet ring cell carcinoma (SRCC) exhibit distinct biological behaviors, yet comprehensive characterization of their clinicopathological features, treatment modalities, and survival disparities remains limited. Leveraging the Surveillance, Epidemiology, and End Results (SEER) database, this population-based study aimed to elucidate these critical aspects. METHODS: We retrospectively analyzed 15,214 patients with American Joint Committee on Cancer (AJCC) stage III/IV gastric (n = 10,203) or colorectal (n = 5011) SRCC diagnosed between 2000 and 2021. Clinicopathological characteristics and survival outcomes were compared across cohorts. Four treatment modalities were evaluated: surgery alone, chemotherapy (CT) alone, surgery + CT, and no therapy. Kaplan-Meier analysis and Cox proportional hazards regression were used to assess overall survival (OS) and cancer-specific survival (CSS). RESULTS: Declining incidence trends were observed for both malignancies. CT alone was the most frequent treatment in gastric SRCC (39.3%), whereas surgery + CT predominated in colorectal SRCC (47.5%). Colorectal SRCC demonstrated significantly superior OS (HR: 0.62, 95% CI: 0.60-0.65, P < 0.001) and CSS (HR: 0.62, 95% CI: 0.60-0.65, P < 0.001) compared to gastric SRCC across all stratified subgroups. The 5-year OS/CSS rates were 6.3%/7.7% for gastric vs. 18.2%/23.0% for colorectal SRCC. Surgery + CT was associated with improved OS and CSS in both gastric and colorectal cohorts, regardless of AJCC stage III/IV. Multivariate analysis identified age, primary site, stage, treatment, and marital status as independent prognosticators. CONCLUSIONS: This study highlights significant clinicopathological and prognostic heterogeneity between advanced gastric and colorectal SRCC, with colorectal tumors demonstrating more favorable outcomes. Surgery + CT may improve survival, highlighting the need for personalized treatment strategies based on the primary tumor site.