Endometriosis and ovarian cancer risk

OBJECTIVE: To critically evaluate the evidence linking endometriosis to ovarian cancer, with particular focus on endometrioid and clear cell histologic subtypes, and to inform risk stratification and patient counseling. METHODS: A systematic review, conducted according to PRISMA guidelines, was used to assess the association between endometriosis and ovarian cancer risk. Additional evidence on molecular, clinical, and therapeutic aspects was synthesized through a multidisciplinary narrative review informed by expert panel discussion. RESULTS: Epidemiological studies consistently demonstrate a modest but statistically significant increase in ovarian cancer risk among women with endometriosis, particularly for endometrioid and clear cell subtypes. Cohort studies report relative risks ranging from 1.3 to 4.2, with the highest estimates observed in women with ovarian endometriomas or deep infiltrating disease. Molecular analyses reveal shared alterations, including mutations in ARID1A, PIK3CA, and PTEN, alongside epigenetic changes and dysregulation of inflammatory and estrogen-dependent pathways, supporting a biological continuum between endometriotic lesions and malignant transformation. Nevertheless, the absolute lifetime risk of ovarian cancer in women with endometriosis remains low (generally <2-5%). Current evidence does not justify routine oncologic surveillance or prophylactic surgery solely based on the diagnosis of endometriosis. CONCLUSIONS: Endometriosis confers a slightly increased relative risk of specific ovarian cancer subtypes; however, the absolute risk remains low for most women, and this distinction is critical to avoid unnecessary anxiety, surveillance, or overtreatment. Individualized risk assessment and prospective studies integrating epidemiologic and molecular data are needed to refine stratification strategies and guide evidence-based care.