The diagnosis of endometrial cancer is confirmed by the histopathology of endometrial curettage/endometrial biopsy. Thorough evaluation of patient, including complete physical examination, and metastatic workup can define the extrauterine spread of the disease within the pelvis or outside the pelvis, in the abdomen, and in supraclavicular or inguinal nodal areas. These patients often have comorbid conditions of obesity, diabetes, and hypertension which require to be evaluated prior to the treatment decision of the disease.

The workup includes imaging ultrasonography (USG), magnetic resonance imaging (MRI), CA125, and PET–CT when indicated. The ultrasonography and magnetic resonance imaging appear to be able to diagnose the myometrial invasion and lymph node metastasis with accuracy of 75–95 % [4–7]. The only way of accurately diagnosing the depth of myometrium invasion is by histological examination of the hysterectomy specimen.

Serum levels of CA125 are elevated in most of the patients with advanced or metastatic endometrial cancer [8]. Multivariate analysis showed lymph node metastasis had the most significant effect on elevation of CA125 levels (>40 u/ml), the sensitivity and specificity for screening lymph node metastasis being 78 % and 84 %, respectively. Thus, preoperative CA125 levels greater than 40 u/ml can be considered as an indication for full surgical staging with pelvic and para-aortic lymphadenectomy in endometrial cancer [9] and may be helpful in monitoring clinical response [10, 11].

The two large prospective surgical staging GOG trials reported in 1984 and 1987 [12, 13] were the landmark trials in defining the prognostic factors of endometrial carcinoma and the current treatment approach for the patients of endometrial cancer.

In addition to intrauterine risk factors of histological type, grade, myometrial invasion, isthmus–cervix extension, and vascular space invasion, the extrauterine factors of adnexal metastasis, intraperitoneal spread, pelvic node metastasis, and para-aortic node metastasis are important in defining the adjuvant treatment. Predicting factors help in selecting the patients who are likely to have advanced disease at presentation and should undergo the extensive surgical staging. The high-risk factors usually modify the survival by either lymph node metastasis or extrauterine spread of the disease.

The following factors can predict the advanced stage of the disease:

The cell type has consistently been recognized as an important factor in predicting the biological behavior of the disease and thus survival. The majority of the uterine corpus tumors are endometrioid adenocarcinoma and usually have relatively good prognosis. Adenocarcinoma with squamous differentiation and villoglandular carcinoma behave similarly with respect to the frequency of nodal metastasis and survival to that in endometrioid adenocarcinoma.

Serous carcinoma often has low survival rates from 40 to 60 % at 5 years [15–22]; clear cell carcinoma also has very aggressive behavior with a reported 5-year survival rate of 30–75 % [23–30] as the disease is often advanced at presentation.

The degree of histological differentiation is considered to be the most sensitive indicators of tumor spread to either lymph nodes or extrauterine sites. High-grade tumors will have deeper myometrial invasion and increased incidence of pelvic and para-aortic nodal metastasis (Table 8.2). More than half of grade 3 lesions are reported to have >50 % myometrial invasion, 30 % involvement of pelvic, and 20 % involvement of the para-aortic lymph nodes. Survival has also been consistently related to histological grade [13].

The depth of myometrial invasion is one of the most important factors, and deep myometrial invasion has high probability of extrauterine disease spread including lymph node metastasis and treatment failure [12, 31, 32].

Site of the tumor within the uterus is important in predicting the nodal metastasis. Fundal lesions have 8 % pelvic nodal metastasis and 4 % para-aortic nodal metastasis. In addition, lower uterine segment lesions will have 16 % risk of positive pelvic node and 14 % risk of positive para-aortic nodes [13].

The lymphatic invasion helps to identify the patients with lymph nodal metastasis and is a strong predictor of tumor recurrence. Vascular space invasion is reported in 15 % of uterus-confined adenocarcinoma [13] with pelvic node positivity in 27 % and para-aortic nodal positivity in 19 %, which is 4–6 times higher in comparison to lymphovascular space-negative patients.

The clinical stage I and occult stage II patients have tumor spread to adnexa in 6 % [13] where pelvic and para-aortic nodal metastasis is reported in 32 % and 20 % cases, respectively, which is four times greater than in patients without adnexal metastasis.

Gross intraperitoneal spread of the disease in absence of adnexal involvement correlates well with higher incidence of involvement of pelvic and para-aortic nodes in about 50 % of patients and 23 % patients, respectively [13, 33, 34]. The pelvic and para-aortic nodal positivity in absence of peritoneal spread is 7 and 4 % only.

The frequency of pelvic and para-aortic nodal metastasis has been correlated well to various pathological risk factors as shown in Table 8.3. Para-aortic nodal metastasis was in 35 % of the cases where pelvic nodes were positive.

Ploidy has remained the strong predictor of disease outcome. Diploid tumors show higher survival rates than aneuploid tumors [35]. Positivity and quantity of estrogen receptors and progesterone receptors have been correlated well with clinical stage, histological grade, absence of vascular invasion, and better outcome [36].