This clinical trial studies positron emission tomography (PET)/computed tomography (CT) and lymph node mapping in finding lymph node metastasis in patients with endometrial cancer that is at high risk of spreading. A PET/CT scan is a procedure that combines the pictures from a PET scan and a CT scan, which are taken at the same time from the same machine. The combined scans give more detailed pictures of areas inside the body than either scan gives by itself. Lymph node mapping uses a radioactive dye, called indocyanine green solution, to identify lymph nodes that may contain cancer cells. PET/CT and sentinel lymph node mapping may be better ways than surgery to identify cancer in the lymph nodes.

PRIMARY OBJECTIVES:

I. To estimate the false negative rate of PET/CT and/or sentinel lymph node mapping in the detection of positive lymph nodes in women with high risk endometrial cancers.

SECONDARY OBJECTIVES:

I. To estimate the sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT and/or sentinel lymph node mapping in the detection of positive lymph nodes in women with high risk endometrial cancer.

II. To determine if a molecular panel of estrogen-induced genes that we have previously identified from retrospective studies correlate with extra-uterine spread including lymph node metastasis at the time of surgical staging for endometrial cancer.

III. To prospectively identify patterns of lymphatic spread of endometrial cancer.

IV. To correlate cancer antigen 125 (CA-125) and WAP four-disulfide core domain 2 (HE4) levels with disease metastasis at the time of surgical staging and to explore the use of other serum biomarkers to predict recurrence.

V. To prospectively collect morbidity and mortality data related to performing lymph node dissection including intra-operative and postoperative complications.

VI. To determine whether metabolic parameters of the primary endometrial tumor on PET including tumor intensity (maximum standard uptake value [SUV] and peak SUV), metabolic tumor volume (obtained at a threshold of 40% of maximum and at a threshold of SUV=3), and total lesion glycolysis (expressed average SUV over the metabolic tumor volume) are predictive of locoregional or metastatic spread, and whether these parameters correlate with CA-125 and HE4 levels.

OUTLINE:

Patients undergo PET/CT prior to surgery. Patients then undergo intraoperative lymph node mapping with indocyanine green solution, given via superficial and deep cervical injection during full lymphadenectomy.

Inclusion Criteria:

• Histologically confirmed high grade endometrial cancer including grade 3 endometroid, serous, clear cell, malignant mixed Mullerian tumor (MMMT) or any mixed tumor containing one of these cell types
• Patients with a grade 1/2 tumors and evidence of deep myometrial invasion or cervical involvement on preoperative imaging or physical exam
• Candidate for surgery
• No evidence of peritoneal disease on preoperative imaging
• Negative pregnancy test if of child-bearing age
• No preoperative treatment for endometrial cancer including radiation or chemotherapy
• Previous hormonal therapy is allowed

Exclusion Criteria:

• Medical co-morbidities making surgery unsafe, as determined by the primary treating physician
• Any contraindications to PET/CT or lymph node mapping (inability to control serum glucose to a value of =< 200 mg/dl for fludeoxyglucose F-18 [FDG]-PET/CT)
• Does not meet histologic criteria
• Evidence of peritoneal or distant metastasis on preoperative imaging
• Baseline creatinine (necessary for imaging studies)