Clinicopathological and Prognostic Characteristics of Gastric-Type Endocervical Adenocarcinoma: A Nested Case–Control Study

Background/Objectives: Gastric-type endocervical adenocarcinoma (G-EAC) is a rare, aggressive, and HPV-independent subtype of cervical cancer with a poor prognosis. Due to its rarity, existing literature is often limited by small sample sizes, which hinders the development of evidence-based clinical management strategies. This study aims to evaluate the clinicopathological features, prognostic factors, and responses to postoperative adjuvant therapy in a large cohort of G-EAC patients compared with those with usual endocervical adenocarcinoma (UEA). Methods: We conducted a nested case–control study within a prospectively maintained surgical cohort at a national referral center in China. The study population included 195 pathologically confirmed G-EAC cases and 765 UEA cases. Patients were followed longitudinally with comprehensive clinical and survival data collection. One-to-one propensity score matching (PSM) was performed to balance demographic, clinical, and treatment variables between the groups. Survival outcomes were compared using Kaplan–Meier analysis, and independent prognostic factors were identified via Cox regression. Results: G-EAC patients demonstrated significantly worse survival outcomes than matched UEA patients, with 3-year progression-free survival (PFS) of 66.1% vs. 79.8% (p = 0.014) and 3-year overall survival (OS) of 74.9% vs. 84.6% (p = 0.033). Parametrial involvement and pelvic lymph node metastasis were identified as independent risk factors for both recurrence and death (p < 0.05). Regarding adjuvant treatment, combined radiotherapy and chemotherapy significantly improved survival compared with single-modality treatments (PFS: 65.2% vs. 43.6%; OS: 74.3% vs. 54.5%; p < 0.05); however, G-EAC remained less responsive to these therapies than UEA. Conclusions: G-EAC exhibits more aggressive clinical behavior and poorer survival outcomes compared to UEA. While combined radiotherapy and chemotherapy offer survival benefits, outcomes remain suboptimal. These findings underscore the urgent need for early detection strategies and the development of more effective targeted therapies for this specific subtype.