Cardiovascular disease is the most common cause of death in patients diagnosed with endometrial cancer because of the early stage of the cancer at diagnosis and the metabolic risk factors.
To detect endometrial cancer, a technique that directly samples the endometrial tissue is mandatory. The Pap smear is not reliable as a screening procedure in endometrial cancer, although a retrospective study found a strong correlation between positive cervical cytology and high-risk disease (i.e., high-grade tumor and deep myometrial invasion)  as well as an increased risk of nodal disease. The degree of tumor differentiation has an important impact on the natural history of this disease and on treatment selection. An increased incidence of endometrial cancer has been found in association with prolonged, unopposed estrogen exposure.[5,6] In contrast, combined estrogen and progesterone therapy prevents the increase in risk of endometrial cancer associated with unopposed estrogen use.[7,8] In some patients, an antecedent history of complex hyperplasia with atypia can be demonstrated. An increased incidence of endometrial cancer has also been found in association with tamoxifen treatment of breast cancer (NSABP-B-14), related to the estrogenic effect of tamoxifen on the endometrium.[9,10] Because of this increase, patients on tamoxifen should have follow-up pelvic examinations and should be examined if there is any abnormal uterine bleeding.
The pattern of spread is partially dependent on the degree of cellular differentiation. Well-differentiated tumors tend to limit their spread to the surface of the endometrium; myometrial extension is less common. In patients with poorly differentiated tumors, myometrial invasion occurs much more frequently. Myometrial invasion is frequently a harbinger of lymph node involvement and distant metastases and is often independent of the degree of differentiation.[11,12] Metastatic spread occurs in a characteristic pattern. Spread to the pelvic and para-aortic nodes is common. When distant metastasis occurs, it most commonly involves the following: