Endometriosis and ovarian cancer: epidemiological evidence, molecular insights, and clinical decision-making.

Abstract

Endometriosis, particularly ovarian endometrioma, is associated with a 2-fold increased risk of ovarian cancer (OC), especially the clear cell and endometrioid subtypes. However, the absolute lifetime risk of OC in women with endometriosis remains relatively low, estimated at 1.9%. This review provides a focused overview of the relationship between these two conditions, addressing epidemiologic data, molecular links, advances in diagnosis, and clinical management. Somatic mutations in ARID1A, PIK3CA, and KRAS are shared between endometriosis and certain OC subtypes, and the nature of the environment typical of ovarian endometriomas suggests a context-specific oncogenic journey. Although advances in imaging, like transvaginal ultrasound and MRI, have improved endometriosis diagnosis, these modalities remain unreliable for identifying malignant transformation. Biomarkers, including CA-125 and HE4, provide additional diagnostic information, although their low specificity limits their role in clinical practice. Hormonal therapies, particularly the long-term use of combined oral contraceptives (COCs), have proven to be highly effective in reducing OC risk in women with endometriosis. This protective effect persists for more than a decade after discontinuation and has been associated with a risk lower than that of the general population. In addition, COC use has been linked to further protective effects against endometrial and colorectal cancers, highlighting its potential value as a cancer prevention strategy, especially for high-risk groups. Surgical management, particularly the excision of ovarian endometriomas, may also confer protection against OC, although this must be balanced against the risks of recurrence and ovarian reserve loss, especially in younger women. Prophylactic salpingo-oophorectomy is recommended for women with known genetic predispositions, but is not routinely indicated for those with endometriosis alone. Emerging evidence highlights the need for personalized risk prediction models that incorporate genetic, clinical, and environmental factors to guide care. Long-term studies are required to assess the impact of conservative versus surgical management on OC risk and overall survival. This review emphasizes the importance of a multidisciplinary approach to the management of endometriosis in relation to OC risk. While the link between endometriosis and OC is well-established, treatment strategies must be tailored to balance cancer prevention, fertility preservation, and quality of life.