Evaluation of the optimal sequence of adjuvant chemotherapy and radiation therapy in the treatment of advanced endometrial cancer

OBJECTIVE: The optimal sequence of adjuvant chemoradiation in the treatment of advanced endometrial carcinoma (EC) remains unclear. We sought to evaluate the outcomes of patients treated with chemoradiation in sandwich fashion (chemotherapy-radiotherapy-chemotherapy; CRC), versus those treated sequentially (chemotherapy-radiotherapy; CR) (radiotherapy-chemotherapy; RC), to determine if there is a survival advantaged associated with a particular treatment sequence. METHODS: A multicenter retrospective analysis of patients with stage III and IV EC from 2000-2018 was conducted. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemoradiation. Differences in the frequencies of adverse events were evaluated using Pearson's χ(2) test. Progression free survival (PFS) and overall survival (OS) rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 152 patients; 36.8% (n=56) CRC, 28.9% (n=44) CR, and 34.2% (n=52) RC. Histology included 44.0% endometrioid, 47.5% serous and 8.5% clear cell tumors. There was no difference in the frequency of histology (p=0.973), stage (p=0.143), cytoreduction status (p=0.932), or treatment delays (p=0.571) between adjuvant therapy sequences. The most frequent location of disease recurrence was abdomen. The median PFS favored CRC versus CR or RC (36-months vs. 22-months and 24-months, respectively) (p=0.038), as did the median OS (48-months vs. 28-months and 34-months, respectively) (p=0.003). CRC demonstrated superiority over CR and RC sequencing in terms 3-year PFS (55% vs. 34% and 37%, respectively) and 3-year OS (71% vs. 50% and 52%, respectively). CONCLUSIONS: Adjuvant chemoradiation delivered in CRC sequence was associated with improvements in both PFS and OS compared to alternant therapy sequencing.