Sequencing of therapy in women with stage III endometrial carcinoma receiving adjuvant combination chemotherapy and radiation.

OBJECTIVE

While women with stage III endometrial cancer are often treated with chemotherapy and external beam radiation, the optimal sequence of these modalities is unknown. We examined the association between the sequence of chemotherapy (CT) and external beam radiation therapy (RT) on survival for women with stage IIIC endometrial carcinoma.

METHODS

The National Cancer Database was used to identify women with stage IIIC endometrial carcinoma treated with adjuvant CT and RT from 2004 to 2015. Patients were stratified based on the sequence of therapy: RT before CT, CT before RT, or concurrent therapy. The association between treatment sequence and mortality was examined through a weighted propensity score analysis.

RESULTS

A total of 6981 patients were identified, including 5116 (73.3%) who received CT before RT, 696 (10.0%) who received RT before CT, and 1169 (16.7%) who received concurrent therapy. The use of CT-RT increased from 39.9% in 2004 to 75.5% in 2015, while use of RT-CT decreased from 34.0% to 4.4% and concurrent therapy decreased from 26.1% to 20.2% over the same period (P < 0.001). Compared to CT-RT, there was no difference in risk of mortality with RT before CT (HR = 1.01; 95% CI, 0.86-1.19) while concurrent therapy was associated with a 47% increased risk of mortality (HR = 1.47; 95% CI, 1.31-1.66). In a sensitivity analysis combining the groups that received RT first (RT before CT or concurrent RT-CT), mortality was 25% higher (HR = 1.25; 95% CI, 1.13-1.39) compared to a strategy of CT followed by RT.

CONCLUSION

Among women with stage IIIC endometrial carcinoma treated with combination chemotherapy and external beam radiation, a strategy employing chemotherapy first is associated with improved survival compared to concurrent therapy.