Long-term risk of gynecologic malignancies in postmenopausal women with vaginal bleeding and benign endometrial lesions: a cohort study.

Objective: This study aims to assess the long-term incidence risk of gynecologic malignancy in postmenopausal women presenting with vaginal bleeding and pathologically confirmed benign endometrial lesions, and to screen for clinical independent risk factors to provide evidence for risk stratification and follow-up management of this population. Methods: We conducted a retrospective cohort study of 696 postmenopausal women presenting with vaginal bleeding who underwent diagnostic endometrial curettage. Histopathological evaluation established the initial diagnosis; patients with initially benign endometrial pathology underwent short-term (3-month) histologic re-evaluation, and eligible individuals were enrolled in long-term clinical follow-up. We compared the distribution of pathological subtypes between initial and follow-up diagnoses and performed univariate Cox regression and multivariate Cox proportional hazards regression analyses to identify independent predictors of gynecologic malignancy. Results: The initial diagnosis rates of endometrial malignancy and precancerous lesions were 15.1% (105/696) and 2.9% (20/696), respectively. Among the 118 patients with initially benign endometrial pathology, 5.1% (6/118) and 7.6% (9/118) were diagnosed with malignancy and precancerous lesions, respectively, within 3 months of initial evaluation. Of the 453 patients eligible for long-term follow-up, 338 completed follow-up (25.4% lost to follow-up), during which 16 incident malignancies and 8 incident precancerous lesions were identified. High-grade serous carcinoma constituted a significantly higher proportion of malignancies detected during follow-up (43.8%) than of those diagnosed initially (6.5%; P < 0.001). Patients with high-grade serous carcinoma had a significantly lower BMI compared with those with endometrioid adenocarcinoma or precancerous lesions (P = 0.008); however, median diagnostic delay did not differ significantly across histologic subtypes (P = 0.850). Univariable Cox regression identified RDW, endometrial thickness, and age as factors associated with the risk of subsequent neoplasia. Multivariable Cox proportional hazards regression analysis confirmed baseline red blood cell distribution width (HR = 1.331, 95% CI: 1.086-1.630, P = 0.009) and endometrial thickness (HR = 4.452, 95% CI: 2.111-9.391, P < 0.001) as independent predictors of gynecologic malignancy. Conclusion: Our findings confirm that postmenopausal women with vaginal bleeding and initial benign endometrial lesions carry higher long-term gynecologic malignancy risk. Given their poor tumor prognosis, standardized screening and long-term surveillance are clinically vital for this high-risk cohort.