Adding radiotherapy (RT) to chemotherapy after surgery improves overall survival (OS) in patients with stage IV endometrial cancer, according to research published in Gynecologic Oncology.

The benefit with RT was observed across all histologies except clear cell carcinoma, and the benefit was greatest when chemotherapy was combined with both external beam RT (EBRT) and vaginal brachytherapy (VBT). 

Researchers used data from the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER) registries to determine whether adding RT to adjuvant chemotherapy after surgery is associated with improved survival in women with stage IV endometrial cancer.

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The analysis included 17,890 patients (NCDB, 12,812; SEER, 5078) with stage IV endometrial cancer diagnosed between 2004 and 2017. Most patients (90.2%) had stage IVB disease, and 9.8% had stage IVA disease. 

The most common histologies in both databases were serous (NCDB, 34.6%; SEER, 33.9%), endometrioid (NCDB, 32.7%; SEER, 34.3%), and carcinosarcoma (NCDB, 17.0%; SEER, 16.3%).

The different treatment categories included chemotherapy alone, chemotherapy with EBRT, chemotherapy with VBT, or chemotherapy with EBRT plus VBT.

In each database, the majority of patients were treated with chemotherapy without RT (NCDB, 78.8%; SEER, 77.0%). When it was combined with chemotherapy, RT was mainly in the form of EBRT (NCDB, 15.8%; SEER, 15.4%).

Patients treated with EBRT in combination with chemotherapy had a decreased risk of death compared with those treated with chemotherapy alone in the NCDB (hazard ratio [HR], 0.75; 95% CI, 0.70-0.79) and the SEER database (HR, 0.85; 95% CI, 0.77-0.94). 

The survival benefit was more pronounced in patients with stage IVA disease in both databases (NCDB: HR, 0.66; 95% CI, 0.55-0.79; SEER: HR, 0.63; 95% CI, 0.46-0.85).

Patients treated with VBT in combination with chemotherapy also had improved survival compared with those treated with chemotherapy alone (NCDB: HR, 0.61; 95% CI, 0.55-0.68; SEER: HR, 0.66; 95% CI, 0.55-0.79). 

The use of both EBRT and VBT in combination with chemotherapy was associated with a significant improvement in survival despite the small number of treated patients from the NCDB (49 patients; HR, 0.23; 95% CI, 0.13-0.41) and the SEER database (165 patients; HR, 0.56; 95% CI, 0.45-0.68).

Although the overall results in both databases suggested that the use of RT in combination with chemotherapy is associated with improved OS, the greatest OS benefit was noted when chemotherapy was combined with EBRT and VBT. 

However, the researchers suggested that VBT alone may be an acceptable alternative with reduced toxicity, and further investigation is needed to determine the optimal treatment paradigm. 


Barrington DA, Fox B, Meade C, Quick A, Felix AS, Chambers LM. Does the addition of radiation improve survival compared to chemotherapy alone in women with stage IV endometrial carcinoma? Analysis of the NCDB and SEER databases. Gynec Oncol. Published online April 22, 2022. doi:10.1016/j.ygyno.2022.04.007