Prognosis and therapeutic navigation in early-onset digestive tract signet ring cell carcinoma: a clinicopathological integrative study

The incidence of early-onset signet ring cell carcinoma (SRCC) of the digestive tract has been increasing; however, its clinicopathological characteristics, treatment modalities, and long-term outcomes remain limited. This study aims to conduct a comprehensive analysis of these aspects utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with digestive tract SRCC between 2000 and 2021 were included and categorized into early-onset (age ≤ 50 years) and late-onset (> 50 years) groups. Clinicopathological characteristics were compared between the two groups. Propensity score matching (PSM) was used to address confounding. Overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier curves and Cox regression analysis. A total of 25,390 patients were enrolled, including 5,133 with early-onset and 20,257 with late-onset SRCC. The early-onset group exhibited significantly higher risks of lymph node (45.3%) and distant (50.6%) metastasis compared to the late-onset group, especially in the colon and rectum ( P < 0.05). The primary treatment modalities included surgery alone, chemotherapy alone, surgery plus chemotherapy, and no/unknown treatment. Predictors of lymph node metastasis included sex, primary site, and T stage; predictors of distant metastasis included sex, race, primary site, T stage, and N stage. The 1-, 3-, 5-, and 10-year OS rates for early-onset SRCC were 54.0%, 28.1%, 21.9%, and 17.8%, respectively; the corresponding CSS rates were 55.2%, 29.6%, 23.6%, and 19.8%. Multivariate analysis revealed that race, primary site, TNM stage, surgery, and marital status as significant OS and CSS predictors. Early-onset SRCC had better OS and CSS compared to late-onset SRCC ( P < 0.001), findings consistently confirmed through PSM analysis at ratios of 1:1, 1:2, and 1:3 for both endpoints. In M0N0 patients, surgery alone was associated with favorable outcomes; in M0N+ patients, surgery alone and surgery plus chemotherapy were associated with comparable outcomes; in M1 patients, surgery plus chemotherapy was associated with improved outcomes. Compared to late-onset SRCC, early-onset SRCC has a higher risk of metastasis but a modestly better CSS, although the survival advantage is attenuated when accounting for competing non-cancer mortality risks. In this observational study, the association between treatment and prognosis varied by disease extent: surgery alone for M0N0, surgery plus chemotherapy for M1, and either strategy for M0N+ showed favorable associations.