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KEY CONCEPTS

  • For women with early-stage, intermediate-risk endometrial cancer, there is no evidence that adjuvant therapy improves overall survival. For women with low-intermediate-risk disease, observation is favored. For women with high-intermediate-risk disease, vaginal cuff brachytherapy is favored.

  • Women with high-risk disease have either serous or clear cell adenocarcinoma (any stage) or have pathologic stage III disease with extrauterine involvement. Adjuvant treatment may involve radiation, chemotherapy, or a combination of the two modalities, based on histology, stage, and other factors

  • Recurrent or metastatic endometrial cancer is associated with a poor prognosis. Clinical trial GOG 209 supports the use of carboplatin and paclitaxel in this setting.

  • Immunotherapy may be considered as second-line treatment for recurrent/metastatic endometrial cancer. Pembrolizumab has a response rate (RR) of 53% for women with mismatch repair–deficient tumors. The combination of pembrolizumab with the tyrosine kinase inhibitor lenvatinib has a RR of 38% among women with microsatellite stable tumors.

  • Targeted therapies with demonstrated efficacy in second-line treatment include single-agent bevacizumab (GOG229E), and the combination of the mTOR inhibitor everolimus with letrozole.

  • Endocrine therapy may also be used to treat metastatic/recurrent endometrial cancer. It tends to be well tolerated with relatively minor side effects, and has modest RRs, ranging from 11% to 24%. Characteristics that improve the likelihood that a patient will have a favorable response to hormone therapy include having a low tumor grade (1 or 2), endometrioid histology, the presence of estrogen and progesterone receptors, having a longer disease-free interval, and being asymptomatic or minimally symptomatic.

EPITHELIAL UTERINE TUMORS

Epidemiology

Endometrial cancer is the most common gynecologic malignancy, and the fourth most common cancer among women in the United States, affecting 1% to 2% of US women.1 Approximately 75% of women diagnosed with endometrial cancer are diagnosed at an early stage and have a 5-year overall survival (OS) of 74% to 91%.2 For women with stage III or IV disease, 5-year OS rates are 57% to 66% and 20% to 26%, respectively.2 This disease primarily affects women in their postmenopausal and perimenopausal years, with an average age at diagnosis of 61 years,2 although 5% to 30% of women are under the age of 50 years.3

Risk Factors

The main risk factors for endometrial cancer are age, obesity, diabetes, and exposure to excess estrogen without adequate opposition by progesterone. This includes the use of exogenous unopposed estrogen therapy, the use of estrogen agonists (such as tamoxifen), and physiologic states that lead to excess endogenous estrogen. Excess endogenous estrogen can be found in women with obesity, chronic anovulation, early age at menarche, nulliparity, late age of menopause, and in the setting of rare estrogen-secreting tumors.

Obesity is a well-established risk factor for the development of endometrial cancer. A meta-analysis of 19 prospective studies showed that for every 5 kg/m2 increase in body mass index (BMI), a ...

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