Perimenopausal management of ovarian endometriosis and associated cancer risk: When is medical or surgical treatment indicated?

Abstract

In women with endometriosis, the lifetime risk of ovarian cancer is increased from 1.4% to about 1.9%. The risk of clear cell and endometrioid ovarian cancer is, respectively, tripled and doubled. Atypical endometriosis, observed in 1-3% of endometriomas excised in premenopausal women, is the intermediate precursor lesion linking typical endometriosis and clear cell/endometrioid tumors. Prolonged oral contraceptive use is associated with a major reduction in ovarian cancer risk among women with endometriosis. Surveillance ± progestogen treatment or surgery should be discussed in perimenopausal women with small, typical endometriomas. In most perimenopausal women with a history of endometriosis but without endometriomas, surveillance instead of risk-reducing bilateral salpingo-oophorectomy seems advisable. Risk-reducing salpingo-oophorectomy might benefit patients at particularly increased risk, but the evidence is inconclusive. Risk profiling models and decision aids may assist patients in their choice. Screening of the general perimenopausal population to detect asymptomatic endometriomas is unlikely to reduce disease-specific mortality.

Distinct molecular pathways in ovarian endometrioid adenocarcinoma with concurrent endometriosis

“…For example, high‐grade OEA without endometriosis may develop from the secretory epithelial cells of the eutopic endometrium and already have a metastatic phenotype by the time it is discovered . On the other hand, OEA with concurrent endometriosis may develop from secretory epithelial of endometriomas and represent a nonmetastatic phenotype . While our results examine the gene expression differences between OEA with and without endometriosis, these differences may be from the unique endometriotic tumor microenvironment or from the unique cell of origin.…”

“…The molecular mechanism of transformation of endometriosis or atypical endometriomas into malignant ovarian cancers is being actively studied. While mutations in the oncogene, KRAS , and ARID1A have been frequently documented in endometriosis‐associated ovarian cancers, these mutations are frequently discovered in deeply infiltrating implants of endometriosis that do not typically progress to ovarian cancer . Thus, the correlation between genotype and clinical phenotype still needs to be determined .…”

“…While mutations in the oncogene, KRAS , and ARID1A have been frequently documented in endometriosis‐associated ovarian cancers, these mutations are frequently discovered in deeply infiltrating implants of endometriosis that do not typically progress to ovarian cancer . Thus, the correlation between genotype and clinical phenotype still needs to be determined . Clinically, it is thought that women with long‐term untreated endometriosis are at highest risk of developing ovarian cancer .…”

“…Thus, the correlation between genotype and clinical phenotype still needs to be determined . Clinically, it is thought that women with long‐term untreated endometriosis are at highest risk of developing ovarian cancer . For example, the protection of combined oral contraceptive therapy on ovarian cancer risk is more robust for women with endometriosis (odds ratio 0.21 [0.08–0.58, p = 0.003] compared to non‐endometriosis population 0.47 [0.37–0.61, p < 0.001]) .…”

“…Further, the cell of origin may predict aggressive disease. For example, high‐grade OEA without endometriosis may develop from the secretory epithelial cells of the eutopic endometrium and already have a metastatic phenotype by the time it is discovered . On the other hand, OEA with concurrent endometriosis may develop from secretory epithelial of endometriomas and represent a nonmetastatic phenotype .…”