It is unclear how to best sequence adjuvant chemotherapy and radiotherapy for advanced endometrial cancer. We studied the outcomes for women treated with chemotherapy before radiotherapy in a chemotherapy-first (chemotherapy for 6 cycles followed radiotherapy) or 'sandwich' approach (chemotherapy for 3 cycles followed by radiotherapy and subsequently chemotherapy for 3 cycles).

Women with stage IIIC endometrial cancer and no gross residual disease treated with chemotherapy before radiotherapy between April 2003 and April 2016 were included. The Kaplan-Meier method was used to estimate recurrence and survival. We performed a meta-analysis of endometrial cancer trials comparing chemotherapy and radiotherapy versus radiotherapy alone.

A total of 102 patients were included. The mean (SD) age was 63.8 (10.6) years; 84 patients received the chemotherapy-first approach and 18 patients received the 'sandwich' approach. Pelvic and para-aortic nodes were removed in 99% and 88.2%, respectively. Among all the patients, we observed 1 pelvic (1%), 1 para-aortic (1%), and 5 vaginal (4.9%) recurrences. At 3 years, for the 'sandwich' and chemotherapy-first approaches, the vaginal recurrence was 11.8% and 4.2%, pelvic recurrence was 0% and 1.5%, para-aortic recurrence was 0% and 1.2%, distant recurrence was 42.9% and 24.4%, and overall survival was 70.3% and 81.7%, respectively. With 'chemotherapy before radiotherapy' 94.9% completed 4+ chemotherapy cycles (vs 71-90% reported in the literature for 'radiotherapy before chemotherapy'). In a meta-analysis of endometrial cancer trials, distant recurrence rates were reduced with 4+ chemotherapy cycles but not with 3 cycles (p=0.01).

Chemotherapy before radiation sequencing for stage IIIC endometrial cancer was associated with a high proportion of patients completing 4+ chemotherapy cycles and low locoregional lymphatic recurrence rate, despite delaying radiotherapy until after 3-6 cycles of chemotherapy and not administering concurrent cisplatin.