Following total abdominal hysterectomy with or without node dissection, no radiation therapy is a reasonable option for patients without residual disease in the hysterectomy specimen, despite a positive prehysterectomy biopsy of any grade.

Following total abdominal hysterectomy with or without node dissection, no radiation therapy is a reasonable option for patients with grade 1 or 2 cancers with either no invasion or <50% myometrial invasion.

Vaginal cuff brachytherapy may be considered in patients with negative node dissection with grade 3 tumor without myometrial invasion.

Vaginal cuff brachytherapy may be considered in patients with negative node dissection with grade 1 or 2 tumors with <50% myometrial invasion and higher-risk features, such as age >60 and/or lymphovascular space invasion.

Vaginal cuff brachytherapy is as effective as pelvic radiation at preventing vaginal recurrence for patients with: (1) grade 1 or 2 tumors with 50% myometrial invasion or (2) grade 3 tumors with <50% myometrial invasion.

Vaginal cuff brachytherapy is preferred to pelvic radiation in patients with the above risk factors, particularly in patients who have had comprehensive nodal assessment.

Patients with grade 3 cancer with ≥50% myometrial invasion or cervical stroma invasion may benefit from pelvic radiation to reduce the risk of pelvic recurrence.

Patients with grade 1 or 2 tumors with ≥50% myometrial invasion may also benefit from pelvic radiation to reduce pelvic recurrence if other risk factors are present, such as age >60 years and/or lymphovascular space invasion. Vaginal brachytherapy may be a better option for patients with these features, especially if surgical staging was adequate, and nodes were negative.

The best available evidence at this time suggests that reasonable options for adjuvant treatment of patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum include external beam radiation therapy, as well as adjuvant chemotherapy. The best evidence for this population supports the use of chemotherapy, but consideration of external beam radiation therapy is reasonable.

Chemotherapy without external beam radiation may be considered for some patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum based on pathologic risk factors for pelvic recurrence.

Radiation therapy without chemotherapy may be considered for some patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum based on pathologic risk factors for pelvic recurrence. Patients receiving chemotherapy seem to have improved survival compared with radiation therapy alone.

Prospective data are lacking to validate the use of vaginal brachytherapy after pelvic radiation, and most retrospective studies show no evidence of a benefit, albeit with small patient numbers. Use of vaginal brachytherapy in patients also undergoing pelvic external beam radiation is not generally warranted, unless risk factors for vaginal recurrence are present.

The best available evidence suggests that concurrent chemoradiation followed by adjuvant chemotherapy is indicated for patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum. Evidence regarding concurrent chemoradiation is limited at this time, and this recommendation is based on expert opinion; we anticipate level-one evidence from upcoming prospective randomized clinical trials (GOG 0258 and PORTEC-3). Chemotherapy may also be considered in certain patients with high-risk early-stage endometrial cancer, and clinical trials addressing this question are under way.

Alternative sequencing strategies with external beam radiation and chemotherapy are also acceptable. Prospective trials have examined sequential radiation therapy and chemotherapy. Evidence supporting sandwich-type therapy is currently limited.