In the United States, endometrial cancer is the most common gynecologic malignancy. Risk factors include obesity and advancing age. As these factors are now more prevalent, the incidence of endometrial cancer continues to rise. Fortunately, patients usually seek medical attention early due to vaginal bleeding, and endometrial biopsy leads quickly to diagnosis. The cornerstone of treatment is hysterectomy with bilateral salpingo-oophorectomy (BSO) and surgical staging that includes lymph node assessment for most women. Of affected women, 67 percent will have stage I disease that is potentially curable by surgery alone, although high-risk stage I patients often receive adjuvant therapy (Siegel, 2019). The 21 percent of patients with regional disease and 8 percent with distant disease typically require multimodality treatment that includes some combination of surgery, chemotherapy, and radiotherapy.
EPIDEMIOLOGY AND RISK FACTORS
From the Surveillance, Epidemiology, and End Results (SEER) Program (2018) database, women in the United States have a 3-percent lifetime risk of developing endometrial cancer. In 2019, an estimated 61,880 new cases and 12,160 associated deaths are expected (Siegel, 2019). Most patients are diagnosed early and subsequently cured. As a result, endometrial cancer is the fourth leading cause of cancer, but only the sixth leading cause of cancer deaths among women.
Endometrial adenocarcinomas are categorized as type I or type II based on histology. Type I, that is, endometrioid type, makes up 80 to 90 percent of all cases (Felix, 2010). The other 10 to 20 percent are type II cancers, namely, the non-endometrioid histologic types that include serous and clear cell adenocarcinomas and carcinosarcoma. Risk factors for developing endometrial cancer are numerous (Table 33-1). Risks specifically for type I cancers are associated with an excess-estrogen environment.
TABLE 33-1Factors Affecting Endometrial Cancer Risk ||Download (.pdf) TABLE 33-1 Factors Affecting Endometrial Cancer Risk
|Raise risk |
Polycystic ovarian syndrome
Long-term, high-dose unopposed menopausal estrogens
Early age of menarche
Late age of natural menopause
North America or northern Europe residence
Higher education or income level
Tamoxifen, high cumulative doses
DM, CHTN, or gallbladder disease
|Lower risk |
Long-term COC use
Of these, obesity is the most common cause of endogenous overproduction of estrogen. Excessive adipose tissue increases peripheral aromatization of androstenedione to estrone. In premenopausal women, elevated estrone levels trigger abnormal feedback in the hypothalamic-pituitary-ovarian axis. The clinical result is oligo- or anovulation. In the absence of ovulation, the endometrium is exposed to virtually continuous estrogen stimulation without subsequent progestational effect and without menstrual shedding.
Unopposed estrogen therapy is the next most important potential inciting factor. Fortunately, the malignant potential of continuously administered estrogen was recognized decades ago (Smith, 1975). Currently, ...